Увійти

Готові списки джерел за темами / APP-CTFs / Статті в журналах

Статті в журналах з теми "APP-CTFs"

Щоб переглянути інші типи публікацій з цієї теми, перейдіть за посиланням: APP-CTFs.

Автор: Grafiati

Опубліковано: 12 травня 2022

Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями

Оберіть тип джерела:

Ознайомтеся з топ-22 статей у журналах для дослідження на тему "APP-CTFs".

Біля кожної праці в переліку літератури доступна кнопка «Додати до бібліографії». Скористайтеся нею – і ми автоматично оформимо бібліографічне посилання на обрану працю в потрібному вам стилі цитування: APA, MLA, «Гарвард», «Чикаго», «Ванкувер» тощо.

Також ви можете завантажити повний текст наукової публікації у форматі «.pdf» та прочитати онлайн анотацію до роботи, якщо відповідні параметри наявні в метаданих.

Переглядайте статті в журналах для різних дисциплін та оформлюйте правильно вашу бібліографію.

1

Vaillant-Beuchot, Loan, Arnaud Mary, Raphaëlle Pardossi-Piquard, Alexandre Bourgeois, Inger Lauritzen, Fanny Eysert, Paula Fernanda Kinoshita, et al. "Accumulation of amyloid precursor protein C-terminal fragments triggers mitochondrial structure, function, and mitophagy defects in Alzheimer’s disease models and human brains." Acta Neuropathologica 141, no. 1 (October 20, 2020): 39–65. http://dx.doi.org/10.1007/s00401-020-02234-7.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Анотація:

AbstractSeveral lines of recent evidence indicate that the amyloid precursor protein-derived C-terminal fragments (APP-CTFs) could correspond to an etiological trigger of Alzheimer’s disease (AD) pathology. Altered mitochondrial homeostasis is considered an early event in AD development. However, the specific contribution of APP-CTFs to mitochondrial structure, function, and mitophagy defects remains to be established. Here, we demonstrate in neuroblastoma SH-SY5Y cells expressing either APP Swedish mutations, or the β-secretase-derived APP-CTF fragment (C99) combined with β- and γ-secretase inhibition, that APP-CTFs accumulation independently of Aβ triggers excessive mitochondrial morphology alteration (i.e., size alteration and cristae disorganization) associated with enhanced mitochondrial reactive oxygen species production. APP-CTFs accumulation also elicit basal mitophagy failure illustrated by enhanced conversion of LC3, accumulation of LC3-I and/or LC3-II, non-degradation of SQSTM1/p62, inconsistent Parkin and PINK1 recruitment to mitochondria, enhanced levels of membrane and matrix mitochondrial proteins, and deficient fusion of mitochondria with lysosomes. We confirm the contribution of APP-CTFs accumulation to morphological mitochondria alteration and impaired basal mitophagy in vivo in young 3xTgAD transgenic mice treated with γ-secretase inhibitor as well as in adeno-associated-virus-C99 injected mice. Comparison of aged 2xTgAD and 3xTgAD mice indicates that, besides APP-CTFs, an additional contribution of Aβ to late-stage mitophagy activation occurs. Importantly, we report on mitochondrial accumulation of APP-CTFs in human post-mortem sporadic AD brains correlating with mitophagy failure molecular signature. Since defective mitochondria homeostasis plays a pivotal role in AD pathogenesis, targeting mitochondrial dysfunctions and/or mitophagy by counteracting early APP-CTFs accumulation may represent relevant therapeutic interventions in AD.

2

Marttinen, Mikael, Catarina B. Ferreira, Kaisa M. A. Paldanius, Mari Takalo, Teemu Natunen, Petra Mäkinen, Luukas Leppänen та ін. "Presynaptic Vesicle Protein SEPTIN5 Regulates the Degradation of APP C-Terminal Fragments and the Levels of Aβ". Cells 9, № 11 (15 листопада 2020): 2482. http://dx.doi.org/10.3390/cells9112482.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Анотація:

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by aberrant amyloid-β (Aβ) and hyperphosphorylated tau aggregation. We have previously investigated the involvement of SEPTIN family members in AD-related cellular processes and discovered a role for SEPTIN8 in the sorting and accumulation of β-secretase. Here, we elucidated the potential role of SEPTIN5, an interaction partner of SEPTIN8, in the cellular processes relevant for AD, including amyloid precursor protein (APP) processing and the generation of Aβ. The in vitro and in vivo studies both revealed that the downregulation of SEPTIN5 reduced the levels of APP C-terminal fragments (APP CTFs) and Aβ in neuronal cells and in the cortex of Septin5 knockout mice. Mechanistic elucidation revealed that the downregulation of SEPTIN5 increased the degradation of APP CTFs, without affecting the secretory pathway-related trafficking or the endocytosis of APP. Furthermore, we found that the APP CTFs were degraded, to a large extent, via the autophagosomal pathway and that the downregulation of SEPTIN5 enhanced autophagosomal activity in neuronal cells as indicated by altered levels of key autophagosomal markers. Collectively, our data suggest that the downregulation of SEPTIN5 increases the autophagy-mediated degradation of APP CTFs, leading to reduced levels of Aβ in neuronal cells.

3

Hao, Candy Yan, Michael S. Perkinton, William Wai-Lun Chan, Ho Yin Edwin Chan, Christopher C. J. Miller, and Kwok-Fai Lau. "GULP1 is a novel APP-interacting protein that alters APP processing." Biochemical Journal 436, no. 3 (May 27, 2011): 631–39. http://dx.doi.org/10.1042/bj20110145.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Анотація:

Altered production of Aβ (amyloid-β peptide), derived from the proteolytic cleavage of APP (amyloid precursor protein), is believed to be central to the pathogenesis of AD (Alzheimer's disease). Accumulating evidence reveals that APPc (APP C-terminal domain)-interacting proteins can influence APP processing. There is also evidence to suggest that APPc-interacting proteins work co-operatively and competitively to maintain normal APP functions and processing. Hence, identification of the full complement of APPc-interacting proteins is an important step for improving our understanding of APP processing. Using the yeast two-hybrid system, in the present study we identified GULP1 (engulfment adaptor protein 1) as a novel APPc-interacting protein. We found that the GULP1–APP interaction is mediated by the NPTY motif of APP and the GULP1 PTB (phosphotyrosine-binding) domain. Confocal microscopy revealed that a proportion of APP and GULP1 co-localized in neurons. In an APP–GAL4 reporter assay, we demonstrated that GULP1 altered the processing of APP. Moreover, overexpression of GULP1 enhanced the generation of APP CTFs (C-terminal fragments) and Aβ, whereas knockdown of GULP1 suppressed APP CTFs and Aβ production. The results of the present study reveal that GULP1 is a novel APP/APPc-interacting protein that influences APP processing and Aβ production.

4

Sivanesan, Senthilkumar, Ravi Mundugaru, and Jayakumar Rajadas. "Possible Clues for Brain Energy Translation via Endolysosomal Trafficking of APP-CTFs in Alzheimer’s Disease." Oxidative Medicine and Cellular Longevity 2018 (October 21, 2018): 1–11. http://dx.doi.org/10.1155/2018/2764831.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Анотація:

Vascular dysfunctions, hypometabolism, and insulin resistance are high and early risk factors for Alzheimer’s disease (AD), a leading neurological disease associated with memory decline and cognitive dysfunctions. Early defects in glucose transporters and glycolysis occur during the course of AD progression. Hypometabolism begins well before the onset of early AD symptoms; this timing implicates the vulnerability of hypometabolic brain regions to beta-secretase 1 (BACE-1) upregulation, oxidative stress, inflammation, synaptic failure, and cell death. Despite the fact that ketone bodies, astrocyte-neuron lactate shuttle, pentose phosphate pathway (PPP), and glycogenolysis compensate to provide energy to the starving AD brain, a considerable energy crisis still persists and increases during disease progression. Studies that track brain energy metabolism in humans, animal models of AD, and in vitro studies reveal striking upregulation of beta-amyloid precursor protein (β-APP) and carboxy-terminal fragments (CTFs). Currently, the precise role of CTFs is unclear, but evidence supports increased endosomal-lysosomal trafficking of β-APP and CTFs through autophagy through a vague mechanism. While intracellular accumulation of Aβ is attributed as both the cause and consequence of a defective endolysosomal-autophagic system, much remains to be explored about the other β-APP cleavage products. Many recent works report altered amino acid catabolism and expression of several urea cycle enzymes in AD brains, but the precise cause for this dysregulation is not fully explained. In this paper, we try to connect the role of CTFs in the energy translation process in AD brain based on recent findings.

5

Lauritzen, I., R. Pardossi-Piquard, A. Bourgeois, A. Bécot, and F. Checler. "Does Intraneuronal Accumulation of Carboxyl-terminal Fragments of the Amyloid Precursor Protein Trigger Early Neurotoxicity in Alzheimer’s Disease?" Current Alzheimer Research 16, no. 5 (May 21, 2019): 453–57. http://dx.doi.org/10.2174/1567205016666190325092841.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Анотація:

Background: Alzheimer’s disease (AD) is associated with extracellular accumulation and aggregation of amyloid β (Aβ) peptides ultimately seeding in senile plaques. Recent data show that their direct precursor C99 (βCTF) also accumulates in AD-affected brain as well as in AD-like mouse models. C99 is consistently detected much earlier than Aβ, suggesting that this metabolite could be an early contributor to AD pathology. C99 accumulates principally within endolysosomal and autophagic structures and its accumulation was described as both a consequence and one of the causes of endolysosomalautophagic pathology, the occurrence of which has been documented as an early defect in AD. C99 was also accompanied by C99-derived C83 (αCTF) accumulation occurring within the same intracellular organelles. Both these CTFs were found to dimerize leading to the generation of higher molecular weight CTFs, which were immunohistochemically characterized in situ by means of aggregate-specific antibodies. Discussion: Here, we discuss studies demonstrating a direct link between the accumulation of C99 and C99-derived APP-CTFs and early neurotoxicity. We discuss the role of C99 in endosomal-lysosomalautophagic dysfunction, neuroinflammation, early brain network alterations and synaptic dysfunction as well as in memory-related behavioral alterations, in triple transgenic mice as well as in newly developed AD animal models. Conclusion: This review summarizes current evidence suggesting a potential role of the β -secretasederived APP C-terminal fragment C99 in Alzheimer’s disease etiology

6

Wang, Bo-Jeng, Guor Mour Her, Ming-Kuan Hu, Yun-Wen Chen, Ying-Tsen Tung, Pei-Yi Wu, Wen-Ming Hsu, et al. "ErbB2 regulates autophagic flux to modulate the proteostasis of APP-CTFs in Alzheimer’s disease." Proceedings of the National Academy of Sciences 114, no. 15 (March 28, 2017): E3129—E3138. http://dx.doi.org/10.1073/pnas.1618804114.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Анотація:

Proteolytic processing of amyloid precursor protein (APP) C-terminal fragments (CTFs) by γ-secretase underlies the pathogenesis of Alzheimer’s disease (AD). An RNA interference screen using APP-CTF [99-residue CTF (C99)]- and Notch-specific γ-secretase interaction assays identified a unique ErbB2-centered signaling network that was predicted to preferentially govern the proteostasis of APP-C99. Consistently, significantly elevated levels of ErbB2 were confirmed in the hippocampus of human AD brains. We then found that ErbB2 effectively suppressed autophagic flux by physically dissociating Beclin-1 from the Vps34–Vps15 complex independent of its kinase activity. Down-regulation of ErbB2 by CL-387,785 decreased the levels of C99 and secreted amyloid-β in cellular, zebrafish, and mouse models of AD, through the activation of autophagy. Oral administration of an ErbB2-targeted CL-387,785 for 3 wk significantly improves the cognitive functions of APP/presenilin-1 (PS1) transgenic mice. This work unveils a noncanonical function of ErbB2 in modulating autophagy and establishes ErbB2 as a therapeutic target for AD.

7

Shinohara, Mitsuru, Naoyuki Sato, Hitomi Kurinami, Daisuke Takeuchi, Shuko Takeda, Motoko Noma, Hiromi Rakugi та Ryuichi Morishita. "Fluvastatin reduces Aβ levels in brain by upregulating APP-CTFs degradation and Aβ clearance". Neuroscience Research 65 (січень 2009): S64. http://dx.doi.org/10.1016/j.neures.2009.09.194.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

8

Xie, Zhongcong, Yuanlin Dong, Uta Maeda, Weiming Xia та Rudolph E. Tanzi. "RNA Interference Silencing of the Adaptor Molecules ShcC and Fe65 Differentially Affect Amyloid Precursor Protein Processing and Aβ Generation". Journal of Biological Chemistry 282, № 7 (14 грудня 2006): 4318–25. http://dx.doi.org/10.1074/jbc.m609293200.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Анотація:

The amyloid precursor protein (APP) and its pathogenic by-product amyloid-β protein (Aβ) play central roles in Alzheimer disease (AD) neuropathogenesis. APP can be cleaved by β-secretase (BACE) and α-secretase to produce APP-C99 and APP-C83. These C-terminal fragments can then be cleaved by γ-secretase to produce Aβ and p3, respectively. p3 has been reported to promote apoptosis, and Aβ is the key component of senile plaques in AD brain. APP adaptor proteins with phosphotyrosine-binding domains, including ShcA (SHC1), ShcC (SHC3), and Fe65 (APBB1), can bind to and interact with the conserved YENPTY motif in the APP-C terminus. Here we have described for the first time the effects of RNA interference (RNAi) silencing of ShcA, ShcC, and Fe65 expression on APP processing and Aβ production. RNAi silencing of ShcC led to reductions in the levels of APP-C-terminal fragments (APP-CTFs) and Aβ in H4 human neuroglioma cells stably overexpressing full-length APP (H4-FL-APP cells) but not in those expressing APP-C99 (H4-APP-C99 cells). RNAi silencing of ShcC also led to reductions in BACE levels in H4-FL-APP cells. In contrast, RNAi silencing of the homologue ShcA had no effect on APP processing or Aβ levels. RNAi silencing of Fe65 increased APP-CTF levels, although also decreasing Aβ levels in H4-FL-APP cells. These findings suggest that pharmacologically blocking interaction of APP with ShcC and Fe65 may provide novel therapeutic strategies against AD.

9

Yang, Chuanbin, Cui-Zan Cai, Ju-Xian Song, Jie-Qiong Tan, Siva Sundara Kumar Durairajan, Ashok Iyaswamy, Ming-Yue Wu, et al. "NRBF2 is involved in the autophagic degradation process of APP-CTFs in Alzheimer disease models." Autophagy 13, no. 12 (December 2, 2017): 2028–40. http://dx.doi.org/10.1080/15548627.2017.1379633.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

10

Matsushima, Takahide, Tadashi Nakaya та Toshiharu Suzuki. "P1-155: Exclusion of phosporylated APP CTFs from membrane region rich in active γ-secretase". Alzheimer's & Dementia 5, № 4S_Part_7 (липень 2009): P223. http://dx.doi.org/10.1016/j.jalz.2009.04.161.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

11

K. Lakshmana, Madepalli, Subhojit Roy, Kaihong Mi, and David E. Kang. "Amyloidogenic Processing of APP in Lipid Rafts." Open Biology Journal 3, no. 1 (March 19, 2010): 21–31. http://dx.doi.org/10.2174/18741967010030100021.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Анотація:

Increased generation of amyloid β peptide (Aβ) derived from amyloid precursor protein (APP) is the primary pathological characteristic of Alzheimer’s disease (AD). However, the sub cellular compartment in which APP undergoes cleavage by secretases to generate Aβ is not precisely known. Compelling evidences suggest that amyloidogenic processing of APP occurs in lipid rafts. An indirect support for lipid raft processing of APP includes the localization of Aβ, APP C-terminal fragments (CTFs), APP holoprotein and secretases in the lipid raft microdomains, although few studies failed to find APP in the lipid rafts. The indirect support also comes from both experimental and clinical studies involving modulation of cholesterol levels and its effect on Aβ generation. Moderate depletion of cholesterol results in significant reduction in Aβ levels and increased dietary intake of cholesterol leads to higher levels of Aβ production suggesting that amyloidogenic processing of APP strongly depends on cholesterol levels and therefore on lipid raft integrity. More convincing evidence that lipid rafts are critical for amyloidogenic processing of APP comes from studies using antibody-mediated co-patching of APP and BACE1 which results in lipid raft association of APP and BACE1 and increased Aβ generation. Further, an endosome/lipid raft targeting of β-secretase inhibitor by sterol-mediated anchoring leading to reduced Aβ generation also suggests that lipid rafts are pivotal for amyloidogenic processing of APP. In the absence of an effective therapy for AD, proteins responsible for delivery of APP to lipid rafts including LRP, RanBP9 and ApoER2 may be excellent therapeutic targets in AD.

12

Kwart, Dylan, Andrew Gregg, Claudia Scheckel, Elisabeth A. Murphy, Dominik Paquet, Michael Duffield, John Fak, Olav Olsen, Robert B. Darnell та Marc Tessier-Lavigne. "A Large Panel of Isogenic APP and PSEN1 Mutant Human iPSC Neurons Reveals Shared Endosomal Abnormalities Mediated by APP β-CTFs, Not Aβ". Neuron 104, № 2 (жовтень 2019): 256–70. http://dx.doi.org/10.1016/j.neuron.2019.07.010.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

13

Kwart, Dylan, Andrew Gregg, Claudia Scheckel, Elisabeth A. Murphy, Dominik Paquet, Michael Duffield, John Fak, Olav Olsen, Robert B. Darnell та Marc Tessier-Lavigne. "A Large Panel of Isogenic APP and PSEN1 Mutant Human iPSC Neurons Reveals Shared Endosomal Abnormalities Mediated by APP β-CTFs, Not Aβ". Neuron 104, № 5 (грудень 2019): 1022. http://dx.doi.org/10.1016/j.neuron.2019.11.010.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

14

Repetto, Emanuela, Claudio Russo, Valentina Venezia, Mario Nizzari, and Gennaro Schettini. "P4-179 BACE1 enhances APP cleavage, CTFS formation and their interaction with SHCA and GRB2 adaptor proteins." Neurobiology of Aging 25 (July 2004): S526. http://dx.doi.org/10.1016/s0197-4580(04)81737-8.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

15

Sergeant, Nicolas, Jean-Philippe David, Danie Champain, Antoine Ghestem, Annick Wattez, and André Delacourte. "Progressive decrease of amyloid precursor protein carboxy terminal fragments (APP-CTFs), associated with tau pathology stages, in Alzheimer's disease." Journal of Neurochemistry 81, no. 4 (May 7, 2002): 663–72. http://dx.doi.org/10.1046/j.1471-4159.2002.00901.x.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

16

Li, Fengling, Guosheng Han, and Kexiang Wu. "Tanshinone IIA Alleviates the AD Phenotypes in APP and PS1 Transgenic Mice." BioMed Research International 2016 (2016): 1–8. http://dx.doi.org/10.1155/2016/7631801.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Анотація:

Therapeutic approach for Alzheimer’s disease (AD) is still deficient. To find active compounds from herbal medicine is of interest in the alleviation of AD symptoms. This study aimed to investigate the protective effects of Tanshinone IIA (TIIA) on memory performance and synaptic plasticity in a transgenic AD model at the early phase. 25–100 mg/kg TIIA (intraperitoneal injection,i.p.) was administered to the six-month-old APP and PS1 transgenic mice for 30 consecutive days. After treatment, spatial memory, synaptic plasticity, and related mechanisms were investigated. Our result showed that memory impairment in AD mice was mitigated by 50 and 100 mg/kg TIIA treatments. Hippocampal long-term potentiation was impaired in AD model but rescued by 100 mg/kg TIIA treatment. Mechanically, TIIA treatment reduced the accumulations of beta-amyloid 1–42, C-terminal fragments (CTFs), and p-Tau in the AD model. TIIA did not affect basal BDNF but promoted depolarization-induced BDNF synthesis in the AD mice. Taken together, TIIA repairs hippocampal LTP and memory, likely, through facilitating the clearance of AD-related proteins and activating synaptic BDNF synthesis. TIIA might be a candidate drug for AD treatment.

17

Shinohara, Mitsuru, Naoyuki Sato, Hitomi Kurinami, Daisuke Takeuchi, Shuko Takeda, Munehisa Shimamura, Toshihide Yamashita, Yasuo Uchiyama, Hiromi Rakugi та Ryuichi Morishita. "Reduction of Brain β-Amyloid (Aβ) by Fluvastatin, a Hydroxymethylglutaryl-CoA Reductase Inhibitor, through Increase in Degradation of Amyloid Precursor Protein C-terminal Fragments (APP-CTFs) and Aβ Clearance". Journal of Biological Chemistry 285, № 29 (14 травня 2010): 22091–102. http://dx.doi.org/10.1074/jbc.m110.102277.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

18

Lauritzen, Inger, Anaïs Bécot, Alexandre Bourgeois, Raphaëlle Pardossi-Piquard, Maria-Grazia Biferi, Martine Barkats та Fréderic Checler. "Targeting γ-secretase triggers the selective enrichment of oligomeric APP-CTFs in brain extracellular vesicles from Alzheimer cell and mouse models". Translational Neurodegeneration 8, № 1 (грудень 2019). http://dx.doi.org/10.1186/s40035-019-0176-6.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Анотація:

Abstract Background We recently demonstrated an endolysosomal accumulation of the β-secretase-derived APP C-terminal fragment (CTF) C99 in brains of Alzheimer disease (AD) mouse models. Moreover, we showed that the treatment with the γ-secretase inhibitor (D6) led to further increased endolysosomal APP-CTF levels, but also revealed extracellular APP-CTF-associated immunostaining. We here hypothesized that this latter staining could reflect extracellular vesicle (EV)-associated APP-CTFs and aimed to characterize these γ-secretase inhibitor-induced APP-CTFs. Methods EVs were purified from cell media or mouse brains from vehicle- or D6-treated C99 or APPswedish expressing cells/mice and analyzed for APP-CTFs by immunoblot. Combined pharmacological, immunological and genetic approaches (presenilin invalidation and C99 dimerization mutants (GXXXG)) were used to characterize vesicle-containing APP-CTFs. Subcellular APP-CTF localization was determined by immunocytochemistry. Results Purified EVs from both AD cell or mouse models were enriched in APP-CTFs as compared to EVs from control cells/brains. Surprisingly, EVs from D6-treated cells not only displayed increased C99 and C99-derived C83 levels but also higher molecular weight (HMW) APP-CTF-immunoreactivities that were hardly detectable in whole cell extracts. Accordingly, the intracellular levels of HMW APP-CTFs were amplified by the exosomal inhibitor GW4869. By combined pharmacological, immunological and genetic approaches, we established that these HMW APP-CTFs correspond to oligomeric APP-CTFs composed of C99 and/or C83. Immunocytochemical analysis showed that monomers were localized mainly to the trans-Golgi network, whereas oligomers were confined to endosomes and lysosomes, thus providing an anatomical support for the selective recovery of HMW APP-CTFs in EVs. The D6-induced APP-CTF oligomerization and subcellular mislocalization was indeed due to γ-secretase blockade, since it similarly occurred in presenilin-deficient fibroblasts. Further, our data proposed that besides favoring APP-CTF oligomerization by preventing C99 proteolysis, γ-secretase inhibiton also led to a defective SorLA-mediated retrograde transport of HMW APP-CTFs from endosomal compartments to the TGN. Conclusions This is the first study to demonstrate the presence of oligomeric APP-CTFs in AD mouse models, the levels of which are selectively enriched in endolysosomal compartments including exosomes and amplified by γ-secretase inhibition. Future studies should evaluate the putative contribution of these exosome-associated APP-CTFs in AD onset, progression and spreading.

19

Lee, Seung-Eun, Daekee Kwon, Nari Shin, Dasom Kong, Nam Gyo Kim, Hee-Yeong Kim, Min-Ji Kim, Soon Won Choi, and Kyung-Sun Kang. "Accumulation of APP-CTF induces mitophagy dysfunction in the iNSCs model of Alzheimer’s disease." Cell Death Discovery 8, no. 1 (January 10, 2022). http://dx.doi.org/10.1038/s41420-021-00796-3.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Анотація:

AbstractMitochondrial dysfunction is associated with familial Alzheimer’s disease (fAD), and the accumulation of damaged mitochondria has been reported as an initial symptom that further contributes to disease progression. In the amyloidogenic pathway, the amyloid precursor protein (APP) is cleaved by β-secretase to generate a C-terminal fragment, which is then cleaved by γ-secretase to produce amyloid-beta (Aβ). The accumulation of Aβ and its detrimental effect on mitochondrial function are well known, yet the amyloid precursor protein-derived C-terminal fragments (APP-CTFs) contributing to this pathology have rarely been reported. We demonstrated the effects of APP-CTFs-related pathology using induced neural stem cells (iNSCs) from AD patient-derived fibroblasts. APP-CTFs accumulation was demonstrated to mainly occur within mitochondrial domains and to be both a cause and a consequence of mitochondrial dysfunction. APP-CTFs accumulation also resulted in mitophagy failure, as validated by increased LC3-II and p62 and inconsistent PTEN-induced kinase 1 (PINK1)/E3 ubiquitin ligase (Parkin) recruitment to mitochondria and failed fusion of mitochondria and lysosomes. The accumulation of APP-CTFs and the causality of impaired mitophagy function were also verified in AD patient-iNSCs. Furthermore, we confirmed this pathological loop in presenilin knockout iNSCs (PSEN KO-iNSCs) because APP-CTFs accumulation is due to γ-secretase blockage and similarly occurs in presenilin-deficient cells. In the present work, we report that the contribution of APP-CTFs accumulation is associated with mitochondrial dysfunction and mitophagy failure in AD patient-iNSCs as well as PSEN KO-iNSCs.

20

Shen, Ruinan, and Chengbiao Wu. "RIN3 Binds to BIN1 and CD2AP to increase APP‐CTFS in early endosomes." Alzheimer's & Dementia 16, S3 (December 2020). http://dx.doi.org/10.1002/alz.047161.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

21

Wu, Qi, Leonardo Cortez, Razieh Kamali-Jamil, Valerie Sim, Holger Wille, and Satyabrata Kar. "Implication of exosomes derived from cholesterol-accumulated astrocytes in Alzheimer's disease pathology." Disease Models & Mechanisms, September 15, 2021. http://dx.doi.org/10.1242/dmm.048929.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Анотація:

Amyloid β (Aβ) peptides generated from the amyloid precursor protein (APP) play a critical role in the development of Alzheimer's disease (AD) pathology. Aβ-containing neuronal exosomes, which represent a novel form of intercellular communication, have been shown to influence function/vulnerability of neurons in AD. Unlike neurons, the significance of exosomes derived from astrocytes remains unclear. In this study, we evaluated the significance of exosomes derived from U18666A-induced cholesterol-accumulated astrocytes in the development of AD pathology. Our results show that cholesterol accumulation decreases exosome secretion, whereas lowering cholesterol level increases exosome secretion from cultured astrocytes. Interestingly, exosomes secreted from U18666A-treated astrocytes contain higher levels of APP, APP-CTFs, soluble APP, APP secretases and Aβ1-40 than exosomes secreted from control astrocytes. Furthermore, we show that exosomes derived from U18666A-treated astrocytes can lead to neurodegeneration, which is attenuated by decreasing Aβ production or by neutralizing exosomal Aβ peptide with an Aβ antibody. These results, taken together, suggest that exosomes derived from cholesterol-accumulated astrocytes can play an important role in trafficking APP/Aβ peptides and influencing neuronal viability in the affected regions of the AD brain.

22

Cai, Cui-Zan, Chuanbin Yang, Xu-Xu Zhuang, Ning-Ning Yuan, Ming-Yue Wu, Jie-Qiong Tan, Ju-Xian Song, et al. "NRBF2 is a RAB7 effector required for autophagosome maturation and mediates the association of APP-CTFs with active form of RAB7 for degradation." Autophagy, June 16, 2020, 1–19. http://dx.doi.org/10.1080/15548627.2020.1760623.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.