Academic literature on the topic 'Parkinson Diseases'

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Journal articles on the topic "Parkinson Diseases"

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Zhunina, Olga A., Nikita G. Yabbarov, Andrey V. Grechko, Shaw-Fang Yet, Igor A. Sobenin, and Alexander N. Orekhov. "Neurodegenerative Diseases Associated with Mitochondrial DNA Mutations." Current Pharmaceutical Design 26, no. 1 (February 25, 2020): 103–9. http://dx.doi.org/10.2174/1381612825666191122091320.

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Mitochondrial dysfunction underlies several human chronic pathologies, including cardiovascular disorders, cancers and neurodegenerative diseases. Impaired mitochondrial function associated with oxidative stress can be a result of both nuclear and mitochondrial DNA (mtDNA) mutations. Neurological disorders associated with mtDNA mutations include mitochondrial encephalomyopathy, chronic progressive external ophthalmoplegia, neurogenic weakness, and Leigh syndrome. Moreover, mtDNA mutations were shown to play a role in the development of Parkinson and Alzheimer’s diseases. In this review, current knowledge on the distribution and possible roles of mtDNA mutations in the onset and development of various neurodegenerative diseases, with special focus on Parkinson’s and Alzheimer’s diseases has been discussed.
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Leupold, Dieter, Lukasz Szyc, Goran Stankovic, Sabrina Strobel, Hans-Ullrich Völker, Ulrike Fleck, Thomas Müller, Matthias Scholz, Peter Riederer, and Camelia-Maria Monoranu. "Melanin and Neuromelanin Fluorescence Studies Focusing on Parkinson’s Disease and Its Inherent Risk for Melanoma." Cells 8, no. 6 (June 15, 2019): 592. http://dx.doi.org/10.3390/cells8060592.

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Parkinson’s disease is associated with an increased risk of melanoma (and vice versa). Several hypotheses underline this link, such as pathways affecting both melanin and neuromelanin. For the first time, the fluorescence of melanin and neuromelanin is selectively accessible using a new method of nonlinear spectroscopy, based on a stepwise two-photon excitation. Cutaneous pigmentation and postmortem neuromelanin of Parkinson patients were characterized by fluorescence spectra and compared with controls. Spectral differences could not be documented, implying that there is neither a Parkinson fingerprint in cutaneous melanin spectra nor a melanin-associated fingerprint indicating an increased melanoma risk. Our measurements suggest that Parkinson’s disease occurs without a configuration change of neuromelanin. However, Parkinson patients displayed the same dermatofluorescence spectroscopic fingerprint of a local malignant transformation as controls. This is the first comparative retrospective fluorescence analysis of cutaneous melanin and postmortem neuromelanin based on nonlinear spectroscopy in patients with Parkinson’s disease and controls, and this method is a very suitable diagnostic tool for melanoma screening and early detection in Parkinson patients. Our results suggest a non-pigmentary pathway as the main link between Parkinson’s disease and melanoma, and they do not rule out the melanocortin-1-receptor gene as an additional bridge between both diseases.
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Rogaeva, E., and J. Hardy. "Gaucher and Parkinson diseases: Unexpectedly related." Neurology 70, no. 24 (June 9, 2008): 2272–73. http://dx.doi.org/10.1212/01.wnl.0000314657.92762.0f.

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Singleton, A. "What does PINK1 mean for Parkinson diseases?" Neurology 63, no. 8 (October 25, 2004): 1350–51. http://dx.doi.org/10.1212/01.wnl.0000144272.53634.49.

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NUNOMURA, AKIHIKO, GEORGE PERRY, JING ZHANG, THOMAS J. MONTINE, ATSUSHI TAKEDA, SHIGERU CHIBA, and MARK A. SMITH. "RNA Oxidation in Alzheimer and Parkinson Diseases." Journal of Anti-Aging Medicine 2, no. 3 (January 1999): 227–30. http://dx.doi.org/10.1089/rej.1.1999.2.227.

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Okun, M. S., M. R. DeLong, J. Hanfelt, M. Gearing, and A. Levey. "Plasma testosterone levels in Alzheimer and Parkinson diseases." Neurology 62, no. 3 (February 9, 2004): 411–13. http://dx.doi.org/10.1212/01.wnl.0000106840.72938.84.

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Zhang, Jing, Izabela Sokal, Elaine R. Peskind, Joseph F. Quinn, Joseph Jankovic, Christopher Kenney, Kathryn A. Chung, Steven P. Millard, John G. Nutt, and Thomas J. Montine. "CSF Multianalyte Profile Distinguishes Alzheimer and Parkinson Diseases." American Journal of Clinical Pathology 129, no. 4 (April 2008): 526–29. http://dx.doi.org/10.1309/w01y0b808emeh12l.

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Tennigkeit, Jenny, Tim Feige, Maria Haak, Carina Hellqvist, Ümran S. Seven, Elke Kalbe, Jaqueline Schwarz, et al. "Structured Care and Self-Management Education for Persons with Parkinson’s Disease: Why the First Does Not Go without the Second—Systematic Review, Experiences and Implementation Concepts from Sweden and Germany." Journal of Clinical Medicine 9, no. 9 (August 28, 2020): 2787. http://dx.doi.org/10.3390/jcm9092787.

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Integrated care is regarded as a key for care delivery to persons with chronic long-term conditions such as Parkinson’s disease. For persons with Parkinson’s disease, obtaining self-management support is a top priority in the context of integrated care. Self-management is regarded as a crucial competence in chronic diseases since the affected persons and their caregivers inevitably take up the main responsibility when it comes to day-to-day management. Formal self-management education programs with the focus on behavioral skills relevant to the induction and maintenance of behavioral change have been implemented as a standard in many chronic long-term conditions. However, besides the example of the Swedish National Parkinson School, the offers for persons with Parkinson’s disease remain fragmented and limited in availability. Today, no such program is implemented as a nationwide standard in Germany. This paper provides (1) a systematic review on structured self-management education programs specifically designed or adopted for persons with Parkinson’s disease, (2) presents the Swedish National Parkinson School as an example for a successfully implemented nationwide program and (3) presents a concept for the design, evaluation and long-term implementation of a future-orientated self-management education program for persons with Parkinson’s disease in Germany.
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OJ, Castejón, Carrero Gonzalez CM, and Lastre G. "Diabetes and Neurologic Diseases in a Developing Country." Journal of Clinical Case Studies Reviews & Reports 2, no. 4 (August 31, 2020): 1–7. http://dx.doi.org/10.47363/jccsr/2020(2)141.

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In the present clinical and observational study we have analyzed sixteen patients with type II diabetes, ranging from 56 to 88 years-old., and showing blood hypertension (84%) %), cardiovascular diseases (43%), memory disorder (43%), Parkinson disease (31%), Headaches (25%),. Sleep disorders (18%), gait disturbances (18%), language disorders (18%), dizziness and vertigo (12%), cervicogenic headache (12%) liver diseases (12%), gastrointestinal disease (12%) arthritis (12%), respiratory diseases (6%), Alzheimer disease (6%), and previous cerebrovascular accident (6%). We have diagnosed six mixed syndromes of diabetes and Parkinson disease (37%), three patients with diabetes and Alzheimer disease (18%) two cases with diabetes, blood hypertension and Alzheimer disease (12%) and two case with diabetes and cervicogenic headaches (12%). The pathophysiological mechanisms involved are described in each case. A relationship of diabetic patient lifestyle with environmental conditions, low socioeconomic status and family history is postulated.
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Toovey, Stephen, Susan S. Jick, and Christoph R. Meier. "Parkinson’s disease or Parkinson symptoms following seasonal influenza." Influenza and Other Respiratory Viruses 5, no. 5 (March 21, 2011): 328–33. http://dx.doi.org/10.1111/j.1750-2659.2011.00232.x.

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Dissertations / Theses on the topic "Parkinson Diseases"

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Franco, Iborra Sandra. "Mitochondrial quality control in neurodegenerative diseases: focus on Parkinson’s disease and Huntington’s disease." Doctoral thesis, Universitat Autònoma de Barcelona, 2018. http://hdl.handle.net/10803/565668.

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Darrerament s’han produït avanços importants que han contribuït al coneixement dels mecanismes de disfunció cel·lular i mort en la malaltia de Parkinson (MP) i en la malaltia de Huntington (MH). Ambdues malalties són trastorns del moviment que es caracteritzen per la pèrdua específica de neurones dels ganglis basals, les neurones dopaminèrgiques de la substància nigra (SN), en el cas de la MP i les neurones espinoses de l’estriat, en el cas de la MH. Malgrat les diferències, ambdues comparteixen processos patològics comuns com la presència de proteïnes malplegades, l’estrés oxidatiu i disfunció mitocondrial. La mitocòndria és la font d’energia principal en les cèl·lules eucariotes, però també és un orgànul dinàmic relacionat amb una gran quantitat de processos cel·lulars. La disrupció de la homeòstasis mitocondrial i la subseqüent disfunció mitocondrial juguen un paper important en la patofisiologia de les malalties neurodegeneratives. El manteniment de la integritat mitocondrial a través de diferents mecanismes de control és crític per a la superviviència neuronal. Aquesta tesi es centra en l’estudi dels mecanismes de control de qualitat mitocondrial en la MP i la MH, per tal d’entendre millor els mecanismes que duen a la mort cel·lular. En el primer capítol, he estudiat el transport de proteïnes a la mitocòndria en models in vitro i in vivo de la MP. In vitro, la inhibició del complexe I produeix una alteració del transport de proteïnes a la mitocòndria així com una disminució dels nivells de proteïnes OXPHOS, acumulació de proteïnes agregades i disminució dels nivells de chaperones mitocondrials. Per tal de restablir el transport de proteïnes mitocondrials es van sobreexpressar dos components clau del sistema de translocases: la translocasa de la membrana externa 20 (TOM20) i la translocasa de la membrana interna 23 (TIM23). La sobreexpressió in vitro de TOM20 i TIM23 va restaurar el transport de proteïnes mitocondrials i va alleugerar la disfunció mitocondrial i la mort cel·lular. La inhibició del complexe I en ratolins també dóna lloc a una alteració del transport de proteïnes mitocondrials i produeix neurodegeneració del sistema dopaminèrgic. La sobreexpressió de TIM23 va restaurar parcialment el transport de proteïnes i va protegir lleugerament les neurones dopaminèrgiques de la SN. En canvi, la sobreexpressió de TOM20 va ser incapaç de millorar el transport de proteïnes mitocondrials i, fins i tot, va exacerbar la mort cel·lular. Aquests resultats posen de relleu el paper de la disfunció del transport de proteïnes mitocondrials, en particular de dos dels seus components, en la patogènesis de la MP i suggereixen la necessitat de futurs estudis es centrin en altres elements d’aquest sistema. En el segon capítol, he estudiat el paper de la proteïna huntingtina en la mitofàgia i com la seva mutació, que dóna lloc a una expansió de glutamines, pot afectar a aquesta funció. Per a tal fi, he treballat en un model in vitro de cèl·lules estriatals ST-Q7 (control) i ST-Q111 (mutant). En condicions fisiològiques, la mitofàgia induïda no es troba mitjançada pel reclutament de parkin als mitocondris despolaritzats. La huntingtina mutada afecta la mitofàgia induïda a través de l’alteració de la seva funció de scaffold en diferents passos del procés de mitofàgia: (i) activació d’ULK1 a través de l’alliberament de mTORC1, (ii) formació del complexe Beclin 1-Vps15,(iii) interacció dels adaptadors de mitofàgia OPTN i NDP52 amb huntingtina i, (iv) amb LC3. Com a resultat, els mitocondris de les cèl·lules ST-Q111 estan més danyats i tenen una respiració mitocondrial deficient. Aquests resultats demostren la presència d’una alteració en la mitofàgia com un mecanisme lligat a la MH. En conclusió, el descobriment de noves dianes mitocondrials en la MP i MH emfatitza el paper important que juga el control de qualitat mitocondrial en la neurodegeneració.
In the past years, several important advances have expanded our understanding of the pathways that lead to cell dysfunction and death in Parkinson’s disease (PD) and Huntington’s disease (HD). Both diseases are movement disorders characterized by the loss of a specific subset of neurons within the basal ganglia, dopaminergic neurons in the substantia nigra pars compacta (SNpc), in the case of PD, and medium spiny neurons in the striatum, in the case of HD,. Despite distinct clinical and pathological features, these two neurodegenerative disorders share critical underlying pathogenic mechanisms such as the presence of misfolded and/or aggregated proteins, oxidative stress and mitochondrial anomalies. Mitochondria are the prime energy source in most eukaryotic cells, but these highly dynamic organelles are also involved in a multitude of cellular events. Disruption of mitochondrial homeostasis and the subsequent mitochondrial dysfunction plays a key role in the pathophysiology of neurodegenerative diseases. Therefore, maintenance of mitochondrial integrity through different surveillance mechanisms is critical for neuronal survival. In this thesis I have studied in depth some mitochondrial quality control mechanisms in the context of PD and HD, in order to broaden the knowledge about the pathomechanisms leading to cell death. In the first chapter I have studied mitochondrial protein import in in vitro and in vivo models of PD. In vitro, complex I inhibition, a characteristic pathological hallmark in PD, impaired mitochondrial protein import. This was associated with OXPHOS protein downregulation, accumulation of aggregated proteins inside mitochondria and downregulation of mitochondrial chaperones. Therefore, we aimed to reestablish the mitochondrial protein import by overexpressing two key components of the system: translocase of the outer membrane 20 (TOM20) and translocase of the inner membrane 23 (TIM23). Overexpression of TOM20 and TIM23 in vitro restored protein import into mitochondria and ameliorated mitochondrial dysfunction and cell death. Complex I inhibition also impaired mitochondrial protein import and led to dopaminergic neurodegeneration in vivo. Overexpression of TIM23 partially rescued protein import into mitochondria and slightly protected dopaminergic neurons in the SNpc. On the contrary, TOM20 overexpression did not rescue protein import into mitochondria and exacerbated neurodegeneration in both SNpc and striatum. These results highlight mitochondrial protein import dysfunction and the distinct role of two of their components in the pathogenesis of PD and suggest the need for future studies to target other elements in the system. In the second chapter, I have studied the role of huntingtin in mitophagy and how the polyglutamine expansion present in mutant huntingtin can affect its function. For such, I worked with differentiated striatal ST-Q7 (as control) and ST-Q111 (as mutant) cells, expressing full length huntingtin. In these conditions, induced mitophagy was not mediated by Parkin recruitment into depolarized mitochondria. Mutant huntingtin impaired induced mitophagy by altering wildtype huntingtin scaffolding activity at different steps of mitophagy process: (i) ULK1 activation through its release from the mTORC1, (ii) Beclin1-Vps15 complex formation, (iii) interaction of the mitophagy adapters OPTN and NDP52 with huntingtin and (iv) with LC3. As a result, mitochondria from ST-Q111 cells exhibited increased damage and altered mitochondrial respiration. These results uncover impaired mitophagy as a potential pathological mechanism linked with HD. In conclusion, we have discovered new mitochondrial targets for PD and HD emphasizing the important role that mitochondrial quality control plays in neurodegeneration
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Luchesi, Karen Fontes 1984. "Dyphagia in amyotrophic lateral sclerosis and in parkinson¿s disease = A disfagia na esclerose lateral amiotrófica e na doença de Parkinson." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311989.

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Orientador: Satoshi Kitamura
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-08-22T11:47:36Z (GMT). No. of bitstreams: 1 Luchesi_KarenFontes_D.pdf: 2231982 bytes, checksum: 2f5ef1dbfa543808275311de510df643 (MD5) Previous issue date: 2013
Resumo: A Doença de Parkinson (DP) é uma das doenças neurodegenerativas mundialmente mais prevalentes. Dentre as doenças do neurônio motor, a Esclerose Lateral Amiotrófica (ELA) é a mais frequente. A qualidade de vida e o prolongamento da expectativa de vida dos sujeitos com doenças neurodegenerativas, como ELA e DP, são foco da intervenção fonoaudiológica, visto que uma das maiores causas de morte são as pneumonias aspirativas. Esta pesquisa teve por objetivo analisar e descrever aspectos relacionados à disfagia e à sua progressão em sujeitos diagnosticados com ELA e DP. Ao todo, participaram 49 sujeitos com ELA e 24 sujeitos com DP. Todos foram avaliados e acompanhados no ambulatório de Otorrinolaringologia/Disfagia do Hospital de Clínicas da Universidade Estadual de Campinas. Foram incluídos no estudo, apenas os sujeitos que estavam em acompanhamento periódico no ambulatório de neurologia do referido hospital e em tratamento medicamentoso. Foram excluídos os sujeitos sem queixa de deglutição ou que apresentassem outras doenças que pudessem causar alteração na deglutição. Todos foram submetidos à entrevista estruturada, videoendoscopia da deglutição, avaliação clínica da deglutição e intervenção fonoaudiológica, além de terem a funcionalidade de ingestão oral classificada pela Functional Oral Intake Scale. Foi realizada uma análise descritiva dos dados com apresentação de frequência das variáveis categóricas e medidas de tendência central e dispersão das variáveis numéricas. Na análise exploratória foram utilizados: Regressão de Cox, teste Exato de Fisher, teste de Kruskal-Wallis, Qui-quadrado, teste de Mann-Whitney e análise de sobrevivência de Kaplan-Meier. As análises foram realizadas por meio do software SPSS versão 13.0 para Windows, tendo sido adotado o nível de significância para os testes estatísticos de 0,05. Na ELA, foi identificado como fator associado à disfagia moderada ou grave, a odinofagia (p=0,01). Foram identificados como fatores que influenciaram na progressão da disfagia na ELA a idade de início da doença (p=0,02) e o início bulbar (p=0,04). A idade de início avançada (p=0,03) e o menor tempo de doença até a primeira avaliação (p=0,004) foram identificados como fatores que levaram à necessidade de indicação de uma via alternativa de alimentação em menor tempo na ELA. Não foram identificados fatores que influenciassem a progressão da disfagia na DP. Observou-se melhora e estabilização da função de deglutição na maioria dos sujeitos com DP estudados. Conclui-se que a idade de início e o início bulbar da ELA são fatores associados à piora rápida da disfagia. Não houve fatores associados à progressão da disfagia na PD e a funcionalidade na deglutição destes pacientes foi caracterizada por melhora e manutenção
Abstract: Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases worldwide. Among the motor neuron diseases, the Amyotrophic Lateral Sclerosis (ALS) is the most common. The quality of life and longer life expectancy for these individuals with neurodegenerative diseases are the purpose of speech-language therapy, as the leading cause of death are aspirative pneumonias. The objective of this study was to analyze and describe aspects related to dysphagia and its progression in patients diagnosed with ALS and PD. Altogether, 49 patients with ALS and 24 patients with PD participated in the study. All patients were evaluated and followed by at the Otolaryngology/Dysphagia services of the Clinical Hospital of the University of Campinas. The study included only patients who have been regularly monitored at the neurology service and undergoing drug treatment. Patients who had other conditions that could cause changes in swallowing or with no complaints concerning swallowing were excluded. All patients underwent a structured interview, Fiberoptic Endoscopic Evaluation of Swallowing, clinical evaluation of swallowing and swallowing management. Furthermore, they had the swallowing functionality classified by the Functional Oral Intake Scale. We performed a descriptive analysis with presenting the frequency of categorical variables, central measures tendency and dispersion of numerical variables. In exploratory data analysis were applied Cox Regression, Kruskal-Wallis, Chi-square, Mann-Whitney and survival analysis of Kaplan-Meier. The analyses were performed using SPSS version 13.0 for Windows and the significance level for statistical tests was 5%. Odynophagia was identified as an associated factor with moderate or severe dysphagia in ALS. The onset age of ALS (p = 0.02) and the bulbar onset ALS (p = 0.04) were identified as factors that influence the progression of dysphagia in ALS. Advanced onset age (p = 0.03) and shorter disease duration (p = 0.004) were identified as factors that lead to sooner need for non-oral feeding. We did not identify any associated factors with the progression of dysphagia in PD. We noticed an improvement and stabilization of the swallowing function in most patients with PD. We conclude that the onset age and bulbar onset of ALS are factors associated with rapid worsened dysphagia
Doutorado
Epidemiologia
Doutora em Saúde Coletiva
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Vilas, Rolán Dolores. "Caracterización clínica, bioquímica y de neuroimagen de la enfermedad de Parkinson asociada a mutaciones del gen LRRK2 y de su fase prodrómica." Doctoral thesis, Universitat de Barcelona, 2016. http://hdl.handle.net/10803/397743.

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La presente memoria se basa en cuatro trabajos que pertenecen a una misma línea de estudio: el estudio de la enfermedad de Parkinson asociada a mutaciones del gen LRRK2 (EP-LRRK2) . En primer lugar, se ha estudiado la EP-LRRK2 desde un punto de vista clínico, centrándonos en los síntomas no motores. En segundo lugar se ha realizado un estudio a través de la sonografía transcraneal en portadores de la mutación G2019S del gen LRRK2 , tanto pacientes con enfermedad de Parkinson como portadores asintomáticos. En tercer lugar, evaluamos la conectividad funcional a través de resonancia magnética en portadores asintomáticos de mutaciones del gen LRRK2 (aLRRK2) . Por último, se ha investigado la capacidad de los biomarcadores en líquido cefalorraquídeo para diferenciar a los portadores de mutaciones del gen LRRK2 de no portadores. Los resultados de esta tesis doctoral apuntan hacia la idea de que la EP-LRRK2, aunque clínicamente similar a la enfermedad de Parkinson idiopática, presenta algunos rasgos diferenciales tanto clínicos, como de neuroimagen y bioquímicos. Asimismo los portadores asintomáticos de mutaciones del gen LRRK2 presentan alteraciones en la neuroimagen, tanto en la sonografía transcraneal como en la resonancia magnética funcional, que preceden el inicio de los síntomas motores en esta población en riesgo de desarrollar EP. A continuación resumimos los resultados más importantes de los cuatro trabajos incluidos en esta tesis doctoral. En el trabajo número 1 (Nonmotor symptoms in LRRK2 G2019S associated Parkinson’s disease) encontramos que los síntomas no motores, como las alteraciones neuropsiquiátricas, disautonómicas y del sueño, son frecuentes en la EP-LRRK2 y que el único síntoma no motor que diferencia la EP-LRRK2 y la EP idiopática es la pérdida de olfato, presente en sólo un 39 % de los pacientes con EP-LRRK2 pero en un 75 % en los pacientes con EP idiopática. Además, una proporción importante de pacientes con EP-LRRK2 percibía que varios síntomas no motores, como la hiposmia, la depresión, el estreñimiento o el exceso de somnolencia diurna, estaban presentes antes del inicio de los síntomas motores, lo que sugiere que estos síntomas pueden caracterizar clínicamente la fase prodrómica del Parkinson LRRK2. En el trabajo número 2 (Clinical and imaging markers in premotor LRRK2 G2019S mutation carriers ) observamos en los pacientes con EP-LRRK2 una hiperecogenicidad de la SN en una proporción similar a los pacientes con EPI y que la hiperecogenicidad de la SN era frecuente en los aLRRK2, sugiriendo que este hallazgo ecográfico podría ser una marcador de la fase premotora de la EP-LRRK2. En el trabajo número 3 (Reduced thalamo-cortical functional connectivity in asymptomatic LRRK2 mutation carriers) encontramos que los aLRRK2 presentaban una disminución en la conectividad funcional entre el tálamo izquierdo y áreas corticales contralaterales, incluyendo el girus postcentral, el girus frontal inferior, el girus temporal medio e inferior, y el córtex occipital, y también entre el caudado izquierdo y el córtex sensitivomotor bilateral. Nuestros hallazgos sugieren también que las alteraciones en la conectividad funcional preceden a los cambios estructurales. Por último, en el trabajo número 4 (Cerebrospinal fluid biomarkers and clinical features in LRRK2 mutation carriers) encontramos que los niveles de α-syn fueron similares entre los pacientes con EP-LRRK2, los aLRRK2 y los familiares asintomáticos no portadores pero significativamente más elevados que en los pacientes con EPI. Por otro lado, no encontramos diferencias entre las concentraciones de Aβ1-42 , T-tau, y p-tau181 entre los grupos de estudio. No detectamos diferencias en las proteínas en LCR entre los aLRRK2 y los familiares no portadores de la mutación, lo que sugiere que las proteínas en LCR no son un buen marcador de la enfermedad en estos.
This thesis is based on four studies that belong to the same line of research: the study of Parkinson’s disease associated with mutations in the LRRK2 gene (LRRK2-PD). First, we studied the LRRK2-PD from a clinical point of view. Secondly, we conducted a study through transcranial sonography in individuals with the G2019S mutation of the LRRK2 gene, both patients with Parkinson's disease as asymptomatic carriers. Third, we assess functional connectivity by means of magnetic resonance imaging in asymptomatic carriers of mutations in the LRRK2 gene (aLRRK2). Finally, we investigated the ability of biomarkers in cerebrospinal fluid to distinguish LRRK2 mutation carriers from noncarriers. In the manuscript Nonmotor symptoms in LRRK2 G2019S associated Parkinson's disease we found that nonmotor symptoms are frequent in LRRK2-PD and the only nonmotor symptom that differentiates LRRK2-PD and idiopathic PD is hyposmia, present in 39% of LRRK2-PD patients but in 75% of idiopathic PD patients. A significant proportion of LRRK2-PD patients perceived that several nonmotor symptoms, such as hyposmia, depression, constipation or excessive daytime sleepiness, were present before the onset of motor symptoms, suggesting that these symptoms can characterize the prodromal phase of LRRK2-PD. In the study entitled Clinical and imaging markers in premotor LRRK2 G2019S mutation carriers we observed that hyperechogenicity of the substantia nigra is frequent in LRRK2-PD and also in asymptomatic LRRK2 mutation carriers, suggesting that this sonographic finding could be a marker of the premotor phase of LRRK2-PD. In work number 3, Reduced thalamo-cortical functional connectivity in asymptomatic LRRK2 mutation carriers, we found that aLRRK2 showed a decrease in functional connectivity between the left thalamus and contralateral cortical areas, that precede structural changes. Finally, in the manuscript Cerebrospinal fluid biomarkers and clinical features in LRRK2 mutation carriers we found that levels of α-syn in CSF were similar among LRRK2-PD, aLRRK2 and noncarriers but significantly higher than in IPD patients. We found no differences between Aβ1-42, T-tau, and p-tau181 among the study groups. We did not detect differences in CSF protein among aLRRK2 and relatives without the mutation, suggesting that CSF proteins are not a good marker of the disease in asymptomatic subjects.
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Gaig, Ventura Carles. "Prevalencia, fenotipo clínico y neuropatológico del parkinsonismo asociado a mutaciones en el gen LRRK2." Doctoral thesis, Universitat de Barcelona, 2011. http://hdl.handle.net/10803/51568.

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Las mutaciones en el gen LRRK2, en especial la G2019S, parecen ser una causa relativamente frecuente de enfermedad de Parkinson (EP).Mutaciones en este gen se detectan en el 5-6% de los casos con EP familiar y en el 1-2 % de los casos esporádicos de diferentes poblaciones occidentales. La mutación R1441G del gen LRRK2 también es una causa frecuente de parkinsonismo en el País Vasco. Las hipótesis del presente trabajo son: 1) En Cataluña las mutaciones G2019S y R1441G del gen LRRK2 son causa de parkinsonismo tanto familiar como esporádico, 2) Las manifestaciones clínicas motoras y no motoras del parkinsonismo asociado a mutaciones en el gen LRRK2 son heterogéneas, y 3) El sustrato neuropatológico del parkinsonismo asociado a mutaciones en el gen LRRK2 es heterogéneo y determina el fenotipo clínico. En relación a estas hipótesis, los objetivos son: 1) Determinar la frecuencia de las mutaciones G2019S y R1441G del gen LRRK2 en pacientes con diagnóstico clínico de EP en un hospital terciario de Barcelona, 2) Definir el fenotipo clínico de los pacientes con EP portadores de una mutación en el gen LRRK2, y 3) Determinar la presencia de las mutaciones G2019S y R1441G del gen LRRK2 en cerebros diagnosticados de EP, de parkinsonimo degenerativo, o de degeneración lobar frontotemporal, y estudiar las características clínicas y patológicas de los casos portadores de una mutación en este gen. Los resultados y conclusiones son: 1) La frecuencia de mutaciones en el gen LRRK2 en pacientes con EP que atienden a una consulta especializada en un hospital terciario de Barcelona es del 5,3%, siendo la mutación G2019S la más frecuente (el 4,3% de los pacientes son portadores). La mutación R1441G es más infrecuente (0,7%). 2) Las mutaciones en el gen LRRK2 son más frecuentes en casos familiares de EP (un 9,6% de los casos son portadores) que en casos esporádicos (un 3,4% son portadores). Hasta en un 43,7% de los pacientes con mutaciones en el gen LRRK2 no existen antecedentes familiares de parkinsonismo. 3) Las características clínicas de los síntomas motores y no motores del parkinsonismo asociado a mutaciones en el gen LRRK2 es indistinguible de los observados en la EP clásica. 4) Las alteraciones neuropatológicas del parkinsonismo asociado a la mutación G2019S del gen LRRK2 son heterogéneas. Si bien el sustrato neuropatológico más frecuente es la patología tipo Lewy, describimos un caso que confirma que uno de los fenotipos neuropatológicos asociados a la mutación G2019S es la degeneración nigral inespecífica sin inclusiones distintivas. 5) No hemos detectado mutaciones en el gen LRRK2 en cerebros asociados a otro tipo de enfermedad neurodegenerativa diferente a la EP, como la demencia por cuerpos de Lewy, la parálisis supranuclear progresiva o la atrofia multisistémica. Su existencia habría que considerarla probablemente excepcional o coincidental.
LRRK2 G2019S mutation is a frequent cause of Parkinson’s disease (PD). This mutation is present in 5-6% of familial PD cases and 1-2 % of sporadic PD patients. LRRK2 R1441G is frequent in PD patients from the Basque country. We hypothesize that 1) In Catalonia, the G2019S and R1441G mutations are frequent in patients with familial as well as sporadic parkinsonism. 2) Clinical features in LRRK2-related parkinsonism are heterogeneous 3) The neuropathological substrate of LRRK2-related parkinsonism is pleomorphic and determines the clinical phenotype. We aim to assess 1) The frequency of the G2019S and R1441G mutations in patients with a clinical diagnosis of PD in Barcelona 2) The clinical phenotype of PD patients carrying a LRRK2 mutation, and 3) The presence of LRRK2 G2019S and R1441G mutations in brains diagnosed of PD, other neurodegenerative parkinsonism, as well as frontotemporal lobar degeneration, and assess the clinical and neuropathological features of those cases carrying a LRRK2 mutation. Results and conclusions: 1) LRRK2 mutations are frequent in PD patients from Barcelona (5.3% of them). The G2019S mutation is more frequent (4.3%) than the R1441G mutation (0.7%). 2) LRRK2 mutations are more frequent in familial PD cases (9.6% of them) than in sporadic cases (3.4%). Family history of parkinsonism is absent in up to 43.7% of patients with LRRK2 mutations. 3) Clinical features of motor and non-motor symptoms of LRRK2-related parkinsonism is indistinguishable from those of classical PD. 4) The neuropathological phenotype of LRRK2 G2019S-related parkinsonism is heterogeneous. Although the most frequent neuropathological substrate is Lewy boby type pathology, we describe a patient with non-specific nigral degeneration and the G2019S mutation. 5) We have not been able to identify LRRK2 mutations in brains of a neurodegenerative disease other than PD (e.g Lewy bodies dementia, Progressive supranuclear palsy or Multiple system atrophy). Presence of LRRK2 mutations in these neurodegenerative diseases would be exceptional or coincidental.
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5

Canal, de la Iglesia Mercè. "Study of pro-apoptotic protein RTP801 homeostasis and its regulation by NEDD4 in Parkinson's disease." Doctoral thesis, Universitat de Barcelona, 2016. http://hdl.handle.net/10803/398915.

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Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons of the Substantia Nigra pars compacta (SNpc) and the presence of cytoplasmic protein inclusions named Lewy Bodies. Current treatments are directed principally to ameliorate the clinical manifestations of the disease rather than suppressing the underlying neuron degeneration and death. This is due, in part, to an incomplete understanding of the pathways that lead to neurodegeneration in PD. RTP801 is induced in cellular and animal models of Parkinson's disease (PD) and is elevated in neuromelanin positive neurons in the Substantia Nigra (SN) of PD patients. In a variety of neuronal systems, RTP801 overexpression or upregulation is sufficient to trigger cell death. This involves a sequential mechanism in which it sequentially inactivates mTOR and survival kinase Akt. RTP801 is a protein with a very short half-life (2-7 minutes), so it should be strictly and dynamically controlled at post-translational level to precisely modulate mTOR pathway. Hence, elucidating which proteins mediate RTP801 degradation would be a stepping-stone to design new therapies to block neurodegeneration. NEDD4, is an E3 ubiquitin ligase highly expressed in mammalian neurons that has been directly linked to PD pathogenesis since it has been reported to promote α-synuclein degradation and to be protective against its toxicity. In this work, we report that NEDD4 contributes to RTP801 protein degradation. We show in neuronal cells that there is a pool of RTP801 degraded via lysosomal pathway. We also demonstrate that both proteins interact and that NEDD4 enhances RTP801 polyubiquitination by preferentially conjugating K63 ubiquitin chains. Importantly, NEDD4 regulates RTP801 protein levels in cultured cells and in a conditional knockout mouse model. We also provide evidence that NEDD4 protects against RTP801 toxicity by mediating its polyubiquitination. Furthermore, NEDD4 levels are decreased in the 6-OHDA PD cellular model and its restoration protects against 6-OHDA-induced cell death by reducing RTP801 protein levels. Moreover, NEDD4 loss of function is toxic in neurons due to RTP801 elevation and the subsequent mTOR/Akt inactivation. A role for NEDD4 in PD is supported by observation of diminished NEDD4 in nigral neurons from postmortem sporadic PD brains. In line with these findings, the NEDD4 signaling inducer NAB2 reduces RTP801 protein levels in control and in 6-OHDA-treated cortical neurons. However, NAB2 is not sufficient to confer protection against 6-OHDA toxicity, because the compound itself represses mTOR signaling pathway compromising cell survival.
RTP801/REDD1 es una proteína pro-apoptótica que se encuentra aumentada en modelos celulares y animales y en muestras humanas de la enfermedad de Parkinson. RTP801 es suficiente y necesaria para promover muerte celular mediante un mecanismo de inhibición de la quinasas de supervivencia mTOR y Akt. NEDD4 es una E3 ubiquitina ligasa que ubiquitiniza proteínas señalizándolas para su posterior degradación. Esta proteína se ha relacionado recientemente con la enfermedad de Parkinson, ya que se ha visto que ubiquitiniza la proteína alfa-sinucleína. En este trabajo, se ha descrito que la RTP801 es un sustrato de la ubiquitina ligasa NEDD4. Se ha demostrado que ambas proteínas interaccionan y que NEDD4 ubiquitiniza RTP801 con cadenas de ubiquitina del tipo K63, señalizándola para su posterior degradación lisosomal. También, se ha observado que NEDD4 regula los niveles de RTP801 en sistemas neuronales, y que la pérdida de función de NEDD4 es tóxica debido al incremento de RTP801 y la consecuente inhibición de las quinasas mTOR/Akt. De forma interesante, la NEDD4 ectópica es capaz de proteger ante la toxicidad provocada por la sobreexpresión de RTP801 y ante la toxina parkinsoniana 6-OHDA. Además, la proteína NEDD4 se encuentra disminuida en neuronas nigrales de la SNpc de cerebros post mortem con la enfermedad de Parkinson. De forma consistente, el compuesto NAB2, un activador de NEDD4, disminuye los niveles de la RTP801 en neuronas. No obstante, la acción de este compuesto no es suficiente para proteger ante la toxicidad de la 6-OHDA. También, se ha identificado una posible regulación entre las E3 ligasas parkina y NEDD4, que conferiría un grado de complejidad mayor a la regulación de la RTP801. Diferentes mutantes de la proteína RTP801 han sido generados para estudiar cómo afecta la ubiquitinización a su estabilidad y función. De forma interesante, el mutante RTP801-K185R pierde la función pro-apoptótica de la RTP801, poniendo en relieve que la ubiquitinización en este residuo es crítica para su función. Finalmente, mediante estudios proteómicos se han identificado numerosos interactores de RTP801 putativos, entre los cuáles se encuentra la clatrina y la proteína adaptadora AP-2, sugiriendo un posible papel de la RTP801 en procesos relacionados con la endocitosis mediada por clatrina.
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Ekstrand, Mats. "Mitochondrial dysfunction in neurodegeneration /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-204-7/.

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Martín, Flores Núria. "Study of the mTOR pathway in neurodegenerative diseases: from synapses to genes." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/665330.

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Huntington's disease (HD) and Parkinson's disease (PD) are devastating neurodegenerative diseases that progress with the death of selective neuronal subpopulations. Neuronal dysfunction and death are consequence of multiple pathogenic processes which alter signalling cascades. The identification of such molecular pathways is crucial to understand the cellular processes that triggers the symptomatology of diseases. One of the common affected pathways in neurodegeneration is the mTOR pathway. It regulates multiple cellular processes to preserve cellular viability and function. Consequently, to maintain a proper function mTOR activity needs to be fine-tuned. RTP801 is an mTOR negative regulator whose action over this pathway plays a significant role in neurodegeneration. RTP801 protein is induced in an attempt to cope cellular stress. However a sustained RTP801 increase leads to neuronal death by sequentially inactivating first mTOR and then Akt pro-survival kinase. RTP801 pathological increase has been involved in neurodegenerative diseases such as PD. Therefore, identifying RTP801 as a possible new therapeutic target in HD would be highly valuable in designing new pharmacological therapies that block, or at least delay, the neurodegeneration and changes in synaptic plasticity associated with it. Our results show that the overexpression of pathogenic N-terminal htt increases RTP801 levels by both lengthening the protein half-life and up-regulating its gene expression. Blockade of RTP801 expression prevents mhtt-induced cell death in HD cellular models. Importantly, RTP801 is elevated in HD-iPSC and putamen, caudate nucleus and cerebellum of human HD post-mortem brain. Although total RTP801 levels in the striatum of HD murine models are not altered, RTP801 is increased in the synaptic compartment which contributes to motor learning deficits in the R6/1 model. Downregulation of striatal RTP801 preserves motor learning skills in R6/1 mice. Hence, RTP801 is identified as a novel downstream effector of mhtt which mediates its toxicity. Recently, exosomes have emerged as a key mechanism to maintain trophic support between neural cells and as vehicle for the clearance of toxic proteins from neurons. Since RTP801 is upregulated under stressful conditions, its propagation by exosomes may allow the neuron-to-neuron spreading of RTP801 toxicity through the modulation of mTOR/Akt pathway. Our results have elucidated a novel function of RTP801 as an exosomal protein. We demonstrate that both ectopic and endogenous RTP801 can be found in exosomes derived from HEK293 cells. In cortical neurons, exosomal RTP801 elevation is sensitive to PD mimetic 6-OHDA (6-hydroxydopamine) but not to potassium depolarization. Consequently, 6-OHDA exposure induces the loading of RTP801 into exosomes released from cortical neurons. Intriguingly, mhtt does not elevate RTP801 in exosomes obtained from a cellular model. In addition, we demonstrate that exosomes have a protective role promoting the activation of both mTOR complex 1 and 2 in recipient neurons, but increased RTP801 counteracts exosomal mTOR pathway activation suggesting that RTP801 negatively modulates pro-survival signals transneuronally. Altered protein functions of the mTOR pathway are a common hallmark in many neurodegenerative diseases. However, little is known about the contribution of genetic variants or single nucleotide polymorphisms (SNPs) that belong to the mTOR pathway. As a multifactorial disease, we studied the association of SNPs in genes encoding mTOR pathway protein components with the susceptibility PD and the response to levodopa (L-DOPA) treatment. The data found indicate that polymorphisms in genetic markers of the mTOR pathway contribute to the susceptibility to PD and the response to L-DOPA treatment in PD patients. We show that these SNPs influence the outcome individually or interacting epistatically with other genetic markers. Taken together, our findings indicate that deregulation of the mTOR signalling pathway plays an important role in the pathogenesis associated with PE and HD and its regulation is crucial to maintain adequate neuronal function and viability.
La enfermedad de Huntington (EH) y la enfermedad de Parkinson (EP) son enfermedades neurodegenerativas devastadoras caracterizadas por la muerte de subpoblaciones neuronales selectivas. La disfunción neuronal y la muerte son consecuencia de múltiples procesos patogénicos que llevan a la alteración de cascadas de señalización. Una de las vías afectadas de forma común en los procesos neurodegenerativos es la vía mTOR. Como modulador de numerosos procesos celulares, la vía de mTOR está regulada para mantener la supervivencia neuronal y la plasticidad sináptica. Una de las proteínas que modula esta cascada de señalización es RTP801. RTP801 se induce en respuesta a factores de estrés celular y su aumento desencadena la muerte neuronal al regular negativamente la vía mTOR/Akt. La implicación de RTP801 en la EP ha sido ampliamente estudiada, sin embargo, su contribución a la patogénesis de la EH nunca antes había sido explorada. Específicamente, nuestros resultados han identificado a RTP801 como un mediador de la toxicidad inducida por huntingtina mutada. El aumento de RTP801 medía la muerte celular inducida por huntingtina mutada y contribuye a la disfunción del aprendizaje motor en el modelo murino R6/1. El silenciamiento de RTP801 en el estriado de los ratones R6/1 contribuye a preservar la plasticidad sináptica de la vía corticoestriatal, y por tanto del aprendizaje motor. Por otra parte, mostramos que los exosomas secretados por neuronas activan la vía de supervivencia mTOR/Akt en neuronas recipientes. Sin embargo, ante un estrés celular, la toxicidad de RTP801 es propagada a través de exosomas que contrarrestan la activación trófica de la vía mTOR/Akt. Finalmente, demostramos que variaciones genéticas en los componentes de la vía de mTOR modulan la susceptibilidad y la edad de inicio de la EP y, contribuyen a la aparición y severidad de la discinesia inducida por levodopa. En conjunto, nuestros hallazgos indican que la desregulación de la vía de mTOR desempeña un papel importante en la patogénesis asociada a la EP y la EH y, su correcta regulación es crucial para mantener la viabilidad y función neuronal.
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Roman, Andrei. "Tau protein aggregation and α-synuclein dysfunction : development of new in vitro and in vivo models to study neurodegenerative diseases." Thesis, Aix-Marseille, 2018. http://www.theses.fr/2018AIXM0281.

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Les signatures histopathologiques de principales maladies neurodégénératives - maladie d'Alzheimer et la maladie de Parkinson - sont les enchevêtrements neurofibrillaires formés par la protéine tau et les corps de Lewy, formés par l'α-synucleine agrégée. Les mécanismes précis du repliement et de l'agrégation de ces protéines, pour la protéine tau comme pour l'α-synucleine, ne sont pas totalement compris à ce jour. Ici, nous nous sommes intéressés à cette question en utilisant des modèles in vitro et in vivo. En étudiant l'agrégation tau in vitro, nous avons mis en évidence un nouvel auto- assemblage réversible de tau, qui dépend de la température et de la présence d’ions zinc, et qui est a priori différent de l'agrégation de tau en présence d'inducteurs d'agrégation tels que l'héparine. Ce processus pourrait néanmoins être impliqué dans les premières étapes de l'agrégation pathologique de tau. Dans une deuxième partie nous avons développé des modèles murin pour étudier les dysfonctionnement de l’α-synucleine. Nous avons montré que l’α-synucleine est directement impliquée dans le développement embryonnaire de régions spécifiques du système nerveux, et qu'elle a des propriétés modulatrices seulement sur les neurones dopaminergiques de la substantia nigra, qui sont touchés dans la maladie de Parkinson.Les résultats obtenus dans nos études de deux protéines qui subissent une agrégation pathogène et forment des inclusions intracellulaires ont contribué à la compréhension des processus moléculaires et cellulaires associés à la dégénérescence neuronale, ce qui fournira de nouvelles pistes pour développer de nouvelles stratégies de thérapies de maladies neurodégénératives
The histopathological hallmarks of the most common neurodegenerative diseases – Alzheimer’s disease and Parkinson’s disease are neurofibrillary tangles formed by tau protein and Lewy bodies inclusions formed by aggregated α-synuclein. The formation and accumulation of these proteins into inclusions cause functional disruptions of the cytoskeleton and leads to neuronal degeneration. The precise mechanisms of tau and synuclein misfolding and aggregation leading to those cellulare incluses, even though very studied, are not fully understood neither for tau protein nor for α-synuclein.Here we have addressed this question using both in vitro and in vivo models. Investigating tau aggregation in vitro, we have found a reversible self-assembly of tau, which depends on temperature and is induced by zinc ions, which is different from the tau aggregation in the presence of aggregation-inducers such as heparin. This process could be implicated in the first steps of tau pathological aggregation. In a second part, we have developed a mouse model for studying the α-synuclein dysfunction. We have shown that α- synuclein is directly involved in the embryonic development of the specific regions of the nervous system, and that it has modulating effect only on the populations of dopaminergic neurons of substantia nigra, which are affected in Parkinson’s disease.Results obtained in our studies of two proteins that undergo pathogenic aggregation and form intracellular inclusions contributed to understanding of molecular and cellular processes associated with neuronal degeneration, which is important for the development of new disease-modifying therapies of neurodegenerative disorders
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Campello, Blasco Laura. "Expression in the mammalian retina of genes and proteins associated with Parkinson and other neurodegenerative diseases." Doctoral thesis, Universidad de Alicante, 2015. http://hdl.handle.net/10045/85191.

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La enfermedad de Parkinson es el segundo trastorno neurodegenerativo más común de nuestra sociedad tras el de Alzheimer. Se caracteriza por una disminución de los niveles del neurotransmisor dopamina asociada a la muerte de las neuronas dopaminérgicas en la substantia nigra del mesencéfalo, proceso que sucede de forma análoga en las células dopaminérgicas de la retina, el subtipo de células amacrinas A18. En consecuencia, además de las múltiples deficiencias motoras y cognitivas que conlleva esta enfermedad, también se han observado alteraciones, a nivel morfológico y fisiológico, en la retina de enfermos de Parkinson y animales modelo de esta enfermedad. Dichas alteraciones incluyen deficiencias en la agudeza visual, sensibilidad al contraste, percepción del color y adaptación a la oscuridad, así como en la detección del movimiento. Sin embargo, se hace necesario esclarecer los mecanismos moleculares subyacentes a esta patología en la retina con el fin de facilitar el diagnóstico molecular y la búsqueda de nuevas dianas terapéuticas. En esta Tesis Doctoral se ha analizado la expresión génica y el patrón de distribución en la retina de distintos mamíferos, desde roedores hasta la especie humana, de dos proteínas de elevada relevancia en la enfermedad de Parkinson, denominadas parkina y UCH-L1, dos importantes componentes del sistema ubicuitina-proteasoma, implicado en la homeostasis proteica celular. En este contexto, se han revisado en profundidad los componentes que integran este sistema en la retina, junto a su papel en el desarrollo y función de este tejido en condiciones fisiológicas y sus alteraciones en condiciones patológicas. Por otra parte, se ha estudiado el patrón de procesamiento ('splicing') alternativo del ARNm del gen PARK2, el cual codifica la proteína parkina, en la retina de mamíferos en condiciones fisiológicas, proceso cuya desregulación está implicada en el desarrollo y progresión de diversas patologías que afectan a la retina, incluida la enfermedad de Parkinson. Adicionalmente, se han investigado las alteraciones a nivel proteico en la retina de monos parkinsonianos tratados con el compuesto neurotóxico MPTP, mediante técnicas de proteómica. Finalmente, se han catalogado y cuantificado todos los genes expresados en la retina adulta humana mediante secuenciación masiva del transcriptoma (RNA-Seq), con especial énfasis en aquellos relacionados con enfermedades neurodegenerativas que afectan a la retina. En conclusión, en esta Tesis Doctoral se ha abordado mediante diferentes aproximaciones experimentales en la retina de mamíferos el estudio de la expresión de los genes y proteínas relacionados con enfermedades neurodegenerativas del sistema nervioso central que cursan con alteraciones en la estructura y función de la retina.
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Domuro, Soriano Carla. "Paper de la proteïna p27 en la regulació de l'expressió de l'α-sinucleïna: Implicacions en la malaltia de Parkinson." Doctoral thesis, Universitat de Barcelona, 2019. http://hdl.handle.net/10803/669150.

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El nostre grup ha identificat prèviament diferents gens i programes transcripcionals regulats per la proteïna p27. En aquest treball ens centrem en el paper de la proteïna p27 en la regulació a nivell transcripcional de l’expressió del gen que codifica per l’α-sinucleïna (gen SNCA), una proteïna molt important en el desenvolupament de la malaltia de Parkinson. Específicament, l’α-sinucleïna forma agregats en regions concretes del cervell. En aquest treball hem comprovat que les cèl·lules deficients de p27 presenten nivells més elevats d’α-sinucleïna. Per altra banda, en cervells de ratolins KO de p27 també observem un augment de l’expressió d’α-sinucleïna. Addicionalment, mitjançant la tècnica de silenciament gènic CRISPR/Cas9 vam obtenir línies cèl·lules KO de p27 i E2F4 i en aquestes cèl·lules també s’observa un augment de l’α-sinucleïna. Posteriorment, hem descrit, mitjançant experiments de ChIP i de luciferases, la regulació a nivell transcripcional de p27 del gen SNCA en associació a diferents factors de transcripció, C/EBPδ i E2F4/p130. En ambdós casos l’expressió de p27 reprimeix l’expressió del gen SNCA. A més a més, mitjançant shRNAs i la tècnica de Proximity Ligation Assay (PLA) hem observat com la disminució dels nivells de p27 i p130 també augmenten l’agregació de l’α-sinucleïna. També hem identificat CDK5 com una possible quinasa encarregada de fosforil·lar a p27 i exportar-ho al citoplasma on no pot exercir la seva funció com a regulador transcripcional. Finalment, mitjançant shRNAs vam disminuir els nivells de CDK5, en aquestes cèl·lules i amb la tècnica de PLA hem aconseguit veure com la supressió de CDK5 provoca un augment en l’agregació de l’α-sinucleïna. Com està descrit que CDK5 és capaç d’interaccionar amb els complexes E2F1/pRB, hem caracteritzat la unió de p27 a E2F1 mitjançant columnes cromatogràfiques i hem establert que E2F1 s’uneix a al extrem final de p27, entre els aminoàcids 160-198, de manera similar a la que s’uneix amb E2F4.
Our group has identified different transcriptional programs regulated by the protein p27. In this work we focus on the role of p27 in the transcriptional regulation of the gene that encodes for α-synuclein (SNCA gene), a very important protein involved in Parkinson’s disease. Specifically, α-synuclein forms aggregates in specific regions of the brain. In this thesis, we found that p27-deficient cells have higher levels of α-synuclein. On the other hand, in brains of p27 KO mice we also observed an increase in α-synuclein levels in some brain regions. Additionally, using the CRISPR/Cas9 gene silencing technique we obtained KO cell lines of p27 and E2F4 and in these cell lines we also observe an increase of α-synuclein. Subsequently, through ChIP and luciferase assays, we described the transcriptional regulation of p27 of the SNCA gene in association with two different transcription factors, C/EBPδ and E2F4/p130. In both cases, p27 expression supresses SNCA expression. Furthermore, using shRNAs and the Proximity Ligation Assay (PLA) technique, we observed how the decrease of p27 and p130 protein levels also increased α-synuclein aggregation levels. We have also identified CDK5 as a kinase that phosphorylates p27 and cause it exportation to cytoplasm where it cannot function as a transcriptional regulator. Finally, using shRNAs we decreased the levels of CDK5 in these cells and with PLA we were able to see how the decrease of CDK5 levels causes an increase in α-synuclein aggregation levels. As it is described that CDK5 can interact with E2F1/pRb complexes, we have characterized the binding of p27 to E2F1 by affinity chromatography assays and we established that, as occurs with E2F4, E2F1 binds to the carboxyl moiety of p27, between aminoacids 160-170.
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Books on the topic "Parkinson Diseases"

1

Understanding Parkinson's disease: [a self help guide]. Omaha, NB: Addicus Books, 1999.

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Cram, David L. Understanding Parkinson's disease: [a self help guide]. Omaha, Neb: Addicus Books, 1999.

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1953-, Gao Xiao Ke, and Schechter Steven 1961-, eds. Understanding Parkinson's disease: A patient's guide to treatment. 2nd ed. Omaha, Neb: Addicus Books, 2009.

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OHOLO Conference on Basic and Therapeutic Strategies in Alzheimer's and Other Related Neuropsychiatric Disorders (30th. 1985 Elat, Israel). Alzheimer's and Parkinson's diseases: Strategies for research and development. New York: Plenum Press, 1986.

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Starkstein, Sergio E. Psychiatric and cognitive disorders in Parkinson Disease. New York: Cambridge University Press, 2002.

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National, Conference on Alzheimer's Disease and Dementia: Problems Prospects and Perspectives (3rd 1988 Detroit Mich ). Alzheimer's and Parkinson's diseases: Recent advances in research and clinical management. New York: Plenum Press, 1989.

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International Conference on Alzheimer's and Parkinson's Diseases: Basic and Therapeutic Strategies (2nd 1989 Kyoto, Japan). Basic, clinical, and therapeutic aspects of Alzheimer's and Parkinson's diseases. New York: Plenum Press, 1990.

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International Conference on Alzheimer's and Parkinson's Diseases: Basic and Therapeutic Strategies (2nd 1989 Kyoto, Japan). Basic, clinical, and therapeutic aspects of Alzheimer's and Parkinson's diseases. New York: Plenum Press, 1990.

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International Conference on Alzheimer's and Parkinson's Diseases: Basic and Therapeutic Strategies (2nd 1989 Kyoto, Japan). Basic, clinical, and therapeutic aspects of Alzheimer's and Parkinson's diseases. New York: Plenum Press, 1990.

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Dieterich, Heinz. Curar en Cuba: Descubrimientos de prevención y curación de sida, cáncer, parkinson, y otras. Tafalla: Txalaparta, 1998.

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Book chapters on the topic "Parkinson Diseases"

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Weis, Serge, Michael Sonnberger, Andreas Dunzinger, Eva Voglmayr, Martin Aichholzer, Raimund Kleiser, and Peter Strasser. "Neurodegenerative Diseases: Parkinson Disease." In Imaging Brain Diseases, 1001–20. Vienna: Springer Vienna, 2019. http://dx.doi.org/10.1007/978-3-7091-1544-2_37.

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Allen, Jacqui E., and Anna Miles. "Parkinson Disease." In Neurologic and Neurodegenerative Diseases of the Larynx, 143–59. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-28852-5_12.

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Miller-Patterson, Cameron, Kathryn E. Krobot, Edward A. Burton, and Libby J. Smith. "Parkinson-Plus Syndromes." In Neurologic and Neurodegenerative Diseases of the Larynx, 161–69. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-28852-5_13.

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Jiang, Hong, Ning Song, Qian Jiao, Limin Shi, and Xixun Du. "Iron Pathophysiology in Parkinson Diseases." In Brain Iron Metabolism and CNS Diseases, 45–66. Singapore: Springer Singapore, 2019. http://dx.doi.org/10.1007/978-981-13-9589-5_4.

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Davids, Joseph, and Hutan Ashrafian. "AIM in Neurodegenerative Diseases: Parkinson and Alzheimer." In Artificial Intelligence in Medicine, 1–15. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-58080-3_190-1.

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Karamat, E., J. Ilmberger, W. Poewe, and F. Gerstenbrand. "Memory dysfunction in Parkinson patients: an analysis of verbal learning processes." In Age-associated Neurological Diseases, 93–97. Vienna: Springer Vienna, 1991. http://dx.doi.org/10.1007/978-3-7091-9135-4_14.

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Tomlinson, Julianna, Valerie Cullen, and Michael G. Schlossmacher. "Identifying Targets in α-Synuclein Metabolism to Treat Parkinson Disease and Related Disorders." In Protein Misfolding Diseases, 817–41. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2010. http://dx.doi.org/10.1002/9780470572702.ch37.

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Dickson, Dennis W., Howard Crystal, Shu-Hui Yen, and Peter Davies. "Alzheimer - Parkinson Disease Spectrum and Diffuse Lewy Body Disease." In Basic, Clinical, and Therapeutic Aspects of Alzheimer’s and Parkinson’s Diseases, 385–90. Boston, MA: Springer New York, 1990. http://dx.doi.org/10.1007/978-1-4684-5844-2_79.

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Gollob, Michael H., Rafeeq Samie, David H. Birnie, Martin S. Green, and Robert M. Gow. "The Wolff-Parkinson-White Syndrome and the Risk of Sudden Death." In Electrical Diseases of the Heart, 55–72. London: Springer London, 2013. http://dx.doi.org/10.1007/978-1-4471-4978-1_5.

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Müller, Martijn L. T. M., and Nicolaas I. Bohnen. "In Vivo Positron Emission Tomography of Extrastriatal Non-Dopaminergic Pathology in Parkinson Disease." In The Neuroimaging of Brain Diseases, 143–70. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-78926-2_7.

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Conference papers on the topic "Parkinson Diseases"

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Martins, Wanghley, and Fábio Henrique Oliveira. "Protótipo de sistema para coleta de dados inerciais com foco na doença de Parkinson." In Encontro Nacional de Computação dos Institutos Federais. Sociedade Brasileira de Computação - SBC, 2020. http://dx.doi.org/10.5753/encompif.2020.11062.

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Currently, the diagnosis and monitoring of people affected by neurodegenerative diseases are made subjectively. Parkinson's disease (PD), for example, is a neurodegenerative disease that affects the motor part of the individual. The evaluation of PD usually is done through scales based on questionnaires. Thus, this research is dedicated to the study and development of a computational system capable of performing the collection, transmission and visual presentation of data related to the human movement, in order to assist the diagnosis and monitoring of PD.
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Baga, Dina, Dimitrios I. Fotiadis, Spiros Konitsiotis, Sofia Tsouli, Maria Diakou, Maria Teresa Arrendondo, Juan Jacobo Estrada, Mario Pansera, and Metin Akay. "PERFORM: A platform for monitoring and management of chronic neurodegenerative diseases: The Parkinson and Amyotrophic Lateral Sclerosis case." In 2009 4th International IEEE/EMBS Conference on Neural Engineering (NER). IEEE, 2009. http://dx.doi.org/10.1109/ner.2009.5109220.

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Wei, Yunyue, Bingquan Zhu, Chen Hou, Chen Zhang, and Yanan Sui. "Interactive Video Acquisition and Learning System for Motor Assessment of Parkinson's Disease." In Thirtieth International Joint Conference on Artificial Intelligence {IJCAI-21}. California: International Joint Conferences on Artificial Intelligence Organization, 2021. http://dx.doi.org/10.24963/ijcai.2021/718.

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Diagnosis and treatment for Parkinson's disease rely on the evaluation of motor functions, which is expensive and time consuming when performing at clinics. It is also difficult for patients to record correct movements at home without the guidance from experienced physicians. To help patients with Parkinson’s disease get better evaluation from in-home recorded movement videos, we developed an interactive video acquisition and learning system for clinical motor assessments. The system provides real-time guidance with multi-level body keypoint tracking and analysis to patients, which guarantees correct understanding and performing of clinical tasks. We tested its effectiveness on healthy subjects, and the efficiency and usability on patient groups. Experiments showed that our system enabled high quality video recordings following clinical standards, benefiting both patients and physicians. Our system provides a novel learning-based telemedicine approach for the care of patients with Parkinson’s disease.
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Cruttenden, Corey, Mahdi Ahmadi, Xiao-Hong Zhu, Wei Chen, and Rajesh Rajamani. "An MRI Compatible Brain Probe for Signal Recording and Deep Brain Stimulation." In 2018 Design of Medical Devices Conference. American Society of Mechanical Engineers, 2018. http://dx.doi.org/10.1115/dmd2018-6951.

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Electrical stimulation of neural tissue is a promising therapy for a variety of neurological diseases. For example, electrical stimulation of deep thalamic nuclei has been used extensively to treat symptoms of Parkinson’s disease, and there is growing interest in treating other conditions including epilepsy and depression with similar techniques. However, the mechanisms of electrical brain stimulation for disease therapy are not fully understood [1].
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Ly, Khoi, Aimee Cloutier, and James Yang. "Quantitative Motor Assessment, Detection, and Suppression of Parkinson’s Disease Hand Tremor: A Literature Review." In ASME 2016 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference. American Society of Mechanical Engineers, 2016. http://dx.doi.org/10.1115/detc2016-59095.

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Parkinson’s disease (PD) is difficult to detect before the onset of symptoms; further, PD symptoms share characteristics with symptoms of other diseases, making diagnosis of PD a challenging task. Without proper diagnosis and treatment, PD symptoms including tremor, bradykinesia, and cognitive problems deteriorate quickly into patients’ late life. Among them, the most distinguishable manifestations of PD are rest and postural tremor. Tremor is defined as an involuntary shaking or quivering movement of the hands or feet. Unified Parkinson’s Disease Rating Scale (UPDRS), Hoehn and Yahr (H&Y) scales are the most common rating scales that quantify the severity of PD. Due to the lack of consistency in these diagnostic tests, researchers are looking for devices for quantification and detection that can provide more objective PD motor assessments. Additionally, since there is currently no cure for PD, temporary PD symptom suppression is an active research area for improving patients’ quality of life. In this survey, the current state of research on Parkinson’s disease hand tremor quantification, detection, and suppression is discussed, especially focusing on electromechanical devices. The future direction of research on these devices is also considered.
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Rudraraju, Sreekanth, and The Nguyen. "Wearable Tremor Reduction Device (TRD) for Human Hands and Arms." In 2018 Design of Medical Devices Conference. American Society of Mechanical Engineers, 2018. http://dx.doi.org/10.1115/dmd2018-6918.

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Parkinson’s disease (PD) and essential tremor (ET) are two common but unrelated diseases that cause movement disorders often involving with severe tremor. The two diseases affects tens of millions of people worldwide, but there is no known cure for them. The tremor not only pose difficulty in completing daily tasks but also impair patients’ social confidence. The objective of this project is to develop a wearable tremor reduction device for the upper limb. The device is obviously different from any previous devices because it is compact, lightweight, comfortable to wear and effective. It is expected to help patients manage the tremor symptoms and regain their normal life.
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Tully, Brett, and Yiannis Ventikos. "Modelling Normal Pressure Hydrocephalus as a ‘Two-Hit’ Disease Using Multiple-Network Poroelastic Theory." In ASME 2010 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2010. http://dx.doi.org/10.1115/sbc2010-19135.

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The evolution of many cerebral diseases such as Alzheimer’s and Parkinson’s Disease, Hydrocephalus, Cerebral Oedema, Stroke, and Tumour are strongly correlated to a change in the transport properties of fluid in the brain. This research proposes a novel application of Multiple-Network Poroelastic Theory (MPET) to investigate cerebral hydrodynamics through a detailed investigation of multiscalar, spatio-temporal transport of fluid between the cerebral blood, cerebrospinal fluid (CSF) and brain parenchyma. Specifically, MPET is used to interrogate the clinical markers of Normal Pressure Hydrocephalus (NPH).
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Zanini, Rafael Anicet, and Esther Luna Colombini. "Parkinson sEMG signal prediction and generation with Neural Networks." In Concurso de Teses e Dissertações da SBC. Sociedade Brasileira de Computação, 2021. http://dx.doi.org/10.5753/ctd.2021.15759.

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Parkinson’s Disease (PD) is a neurodegenerative disorder characterized by symptoms like resting and action tremors, which cause severe impairments to the patient’s life. Recently, many assistance techniques have been proposed to minimize the disease’s impact on patients’ life. However, most of these methods depend on data from PD’s surface electromyography (sEMG), which is scarce. In this work, we propose the first methods, based on Neural Networks, for predicting, generating, and transferring the style of patient-specific PD sEMG tremor signals. This dissertation contributes to the area by i) comparing different NN models for predicting PD sEMG signals to anticipate resting tremor patterns ii) proposing the first approach based on Deep Convolutional Generative Adversarial Networks (DCGANs) to generate PD’s sEMG tremor signals; iii) applying Style Transfer (ST) for augmenting PD’s sEMG signals with publicly available datasets of non-PD subjects; iv) proposing metrics for evaluating the PD’s signal characterization in sEMG signals. These new data created by our methods could validate treatment approaches on different movement scenarios, contributing to the development of new techniques for tremor suppression in patients.
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Ranchet, Maud, Mark Tant, Abiodun E. Akinwuntan, and Hannes Devos. "Comorbidities in Drivers with Parkinson Disease." In Driving Assessment Conference. Iowa City, Iowa: University of Iowa, 2015. http://dx.doi.org/10.17077/drivingassessment.1549.

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Kim, Jung Hwan, Thomas H. Mareci, and Malisa Sarntinoranont. "Computational Model of Interstitial Transport in the Rat Brain Using Diffusion Tensor Imaging." In ASME 2007 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2007. http://dx.doi.org/10.1115/sbc2007-176633.

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In spite of the high therapeutic potential of macromolecular drugs, it has proven difficult to apply them to recovery after injury and treatment of cancer, Parkinson’s disease, and other neurodegenerative diseases. One barrier to systemic administration is low capillary permeability, i.e., the blood-brain and blood-spinal cord barrier. To overcome this barrier, convection-enhanced delivery (CED) infuses agents directly into tissue to supplement diffusion and increase the distribution of large molecules in the brain [1,2]. Predictive models of distribution during CED would be useful in treatment optimization and planning. To account for large infusion volumes, such models should incorporate tissue boundaries and anisotropic tissue properties.
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Reports on the topic "Parkinson Diseases"

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Liu, Liushu, and Zhiyou Cai. Association between cerebral small diseases and the risk of Parkinson disease: a systematic review and meta analysis. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, August 2021. http://dx.doi.org/10.37766/inplasy2021.8.0083.

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Trimble, Brian A. Alaska Native Parkinson's Disease Registry. Fort Belvoir, VA: Defense Technical Information Center, November 2008. http://dx.doi.org/10.21236/ada493391.

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Beal, M. F. Oxidative Damage in Parkinson's Disease. Fort Belvoir, VA: Defense Technical Information Center, January 2005. http://dx.doi.org/10.21236/ada434051.

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Trimble, Brian A. Alaska Native Parkinson's Disease Registry. Fort Belvoir, VA: Defense Technical Information Center, November 2010. http://dx.doi.org/10.21236/ada609645.

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Seroogy, Kim B., and David M. Yurek. Neuregulins, Neuroprotection and Parkinson's Disease. Fort Belvoir, VA: Defense Technical Information Center, December 2002. http://dx.doi.org/10.21236/ada415998.

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Beal, M. F. Oxidative Damage in Parkinson's Disease. Fort Belvoir, VA: Defense Technical Information Center, October 2001. http://dx.doi.org/10.21236/ada416957.

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Trimble, Brian A. Alaska Native Parkinson's Disease Registry. Fort Belvoir, VA: Defense Technical Information Center, June 2011. http://dx.doi.org/10.21236/ada609150.

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Trimble, Brian A. Alaska Native Parkinson's Disease Registry. Fort Belvoir, VA: Defense Technical Information Center, November 2009. http://dx.doi.org/10.21236/ada511588.

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Nelson, Lorene M. Military Service and Parkinson's Disease. Fort Belvoir, VA: Defense Technical Information Center, May 2013. http://dx.doi.org/10.21236/ada583477.

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Tanner, Caroline M. Alaska Native Parkinson's Disease Registry. Fort Belvoir, VA: Defense Technical Information Center, July 2012. http://dx.doi.org/10.21236/ada562185.

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