Journal articles: 'Sortitio'

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Biville, Frédérique. "Sors, sortiri, sortitio. Pratiques et lexique du tirage au sort dans le monde romain." Participations Hors Série, HS (2019): 139. http://dx.doi.org/10.3917/parti.hs01.0139.

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Olesti Vila, Oriol, and Marc Mayer. "La sortitio de Ilici. Del documento epigráfico al paisaje histórico." Dialogues d'histoire ancienne 27, no. 1 (2001): 109–30. http://dx.doi.org/10.3406/dha.2001.2439.

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Ioannidopoulos, Grégory. "M. Aemilius Scaurus et P. Plautius Hypsaeus: Pompée et ses questeurs entre 67 et 61." L'antiquité classique 86, no. 1 (2017): 97–113. http://dx.doi.org/10.3406/antiq.2017.3909.

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M. Aemilius Scaurus (pr. 56) et P. Plautius Hypsaeus (pr. 55) furent des proches de Pompée, auquel ils doivent une bonne partie de leur cursus, notamment une questure orientale qui ouvrit la voie à leurs carrières politiques, dont Pompée n’était jamais absent. En examinant en détail la vie de ces deux hommes et les pratiques de leur époque, plusieurs éléments ont été dégagés qui suggèrent de dater leurs questures non seulement de façon concomitante, mais surtout un peu plus tôt que généralement admis. Car elles pourraient bien être tombées en 67, en vertu de la lex Gabinia. Ainsi, Scaurus et Hypsaeus illustrent la façon dont Pompée concevait ses rapports avec ses questeurs, préférant la sélection extra sortem. En la matière, une rapide comparaison avec les pratiques de Sylla et César suggère une évolution majeure au Ier s. av. J.-C., marquée par le mépris des règles républicaines de la sortitio.

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Bouricius, Terrill. "Why Hybrid Bicameralism Is Not Right for Sortition." Politics & Society 46, no. 3 (August 13, 2018): 435–51. http://dx.doi.org/10.1177/0032329218789893.

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Structural problems are examined with pairing two chambers, one selected by election and the other by sortition, into a traditional bicameral system. It is argued that an all-purpose legislative chamber modeled on existing elected chambers is a mismatch for sortition and that purported benefits of maintaining partisan elections alongside sortition are illusory. Alleged benefits of a hybrid bicameral system are shown to be outweighed by a variety of harmful effects. Furthermore, even if those harms are not substantiated, the continued existence of an elected chamber will likely result in the delimitation of the sortition chamber. Combining many different sorts of minipublics with different characteristics and functions is preferable, and a possible multibody sortition legislative system is presented. Finally, an alternative way forward for sortition is proposed by peeling away individual topic areas from elected bodies and transferring them to sortition bodies.

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Gastil, John, and Erik Olin Wright. "Legislature by Lot: Envisioning Sortition within a Bicameral System." Politics & Society 46, no. 3 (August 13, 2018): 303–30. http://dx.doi.org/10.1177/0032329218789886.

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In this article, we review the intrinsic democratic flaws in electoral representation, lay out a set of principles that should guide the construction of a sortition chamber, and argue for the virtue of a bicameral system that combines sortition and elections. We show how sortition could prove inclusive, give citizens greater control of the political agenda, and make their participation more deliberative and influential. We consider various design challenges, such as the sampling method, legislative training, and deliberative procedures. We explain why pairing sortition with an elected chamber could enhance its virtues while dampening its potential vices. In our conclusion, we identify ideal settings for experimenting with sortition.

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Wright, Erik Olin. "Postscript to Gastil and Wright: The Anticapitalist Argument for Sortition." Politics & Society 46, no. 3 (August 13, 2018): 331–35. http://dx.doi.org/10.1177/0032329218789887.

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Sonnert, Gerhard. "Give Chance a Chance: An Alternative Process for Selecting U.S. Supreme Court Justices." Alternatives: Global, Local, Political 45, no. 1 (February 2020): 33–49. http://dx.doi.org/10.1177/0304375419901220.

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This article develops the proposal that U.S. Supreme Court Justices should be selected by sortition. The greatest threat to the legitimacy of the Supreme Court emanates from ever more politicized selection contests under the current system. Removing politics from Supreme Court recruitment is therefore crucial, and sortition is argued to be a suitable vehicle for accomplishing this. The proposal is motivated through a wider discussion of sortition and democracy.

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Owen, David, and Graham Smith. "Sortition, Rotation, and Mandate: Conditions for Political Equality and Deliberative Reasoning." Politics & Society 46, no. 3 (August 13, 2018): 419–34. http://dx.doi.org/10.1177/0032329218789892.

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The proposal to create a chamber selected by sortition would extend this democratic procedure into the legislative branch of government. However, there are good reasons to believe that, as currently conceived by John Gastil and Erik Olin Wright, the proposal will fail to realize sufficiently two fundamental democratic goods, namely, political equality and deliberative reasoning. It is argued through analysis of its historic and contemporary application that sortition must be combined with other institutional devices, in particular, rotation of membership and limited mandate, in order to be democratically effective and to realize political equality and deliberative reasoning. An alternative proposal for a responsive sortition legislature is presented as more realistic and utopian: one that increases substantially the number of members, makes more extensive use of internal sortition and rotation, and recognizes the importance of establishing limited mandates.

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Mulvad, Andreas Møller, and Benjamin Ask Popp-Madsen. "Sortition-infused democracy: Empowering citizens in the age of climate emergency." Thesis Eleven 167, no. 1 (November 15, 2021): 77–98. http://dx.doi.org/10.1177/07255136211056997.

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This article addresses two great global challenges of the 2020s. On one hand, the accelerating climate crisis and, on the other, the deepening crisis of representation within liberal democracies. As temperatures and water levels rise, rates of popular confidence in existing democratic institutions decline. So, what is to be done? This article discusses whether sortition – the ancient Greek practice of selecting individuals for political office through lottery – could serve to mitigate both crises simultaneously. Since the 2000s, sortition has attracted growing interest among activists and academics. Recently it has been identified in countries like the UK and France as a mechanism for producing legitimate political answers to the climate challenge. However, few theoretical reflections on the potentials and perils of sortition-based climate governance have yet emerged. This article contributes to filling the gap. Based on a critique of the first successful case of sortition used to enhance national environmental policy – in Ireland in 2017–18 – we argue that sortition-based deliberation could indeed speed up meaningful climate action whilst improving the health of democratic systems. However, this positive outcome is not preordained. Success depends not only on green social movements getting behind climate sortition but also on developing flexible, context-specific designs that identify adequate solutions to a number of problems, including those of power (providing citizens’ assemblies with clear agenda-setting prerogatives beyond non-binding consultation); expertise (allowing assembly participants to influence which stakeholders and experts to solicit inputs from); and participation (engaging wider parts of the citizenry in the deliberative process).

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Abbas, Nabila, and Yves Sintomer. "Three Contemporary Imaginaries of Sortition." Common Knowledge 28, no. 2 (May 1, 2022): 242–60. http://dx.doi.org/10.1215/0961754x-9809207.

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Abstract A contribution to the Common Knowledge symposium “Antipolitics,” this article examines the diverse types of imaginary that support sortition, which is currently at the heart of important debates on the reform of existing democratic institutions. Different and often diametrically opposed actors now advocate sortition as a tool for addressing crises of political representation. How are we to understand this convergence? Over the past two decades, the field of experience and the horizon of expectation of citizens in the global North have profoundly changed, and this article seeks to assess those changes in the context of three ideal types that advocate the use of randomly selected minipublics. This article analyzes, each in turn, the attraction of sortition for supporters and theorists of deliberative democracy, antipolitical democracy, and radical democracy, outlining the elements that unite and divide these imaginaries to help explain the astonishing convergence of voices in defense of sortition in politics.

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Courant, Dimitri. "Pensar el sorteo. Modos de selección, marcos deliberativos y principios democráticos." Daímon, no. 72 (November 7, 2017): 59. http://dx.doi.org/10.6018/daimon/295921.

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¿Cómo pensar el sorteo con eficacia? Mi propuesta es construir una teoría general del sorteo, abordándolo de forma comparativa, para averiguar cuáles son las constantes teóricas entre la gran diversidad empírica de sus usos particulares.En primer lugar, comparo el sorteo a los otros tres modos de selección: elección, nombramiento o cooptación y certificación. En segundo lugar, analizo los marcos deliberativos, es decir, “quién decide qué y cómo”. Tercero, distingo cuatro principios democráticos del sorteo: igualdad, imparcialidad, representatividad y legitimidad. Mi primera hipótesis es que el sorteo amplía considerablemente la igualdad, imparcialidad y representatividad. La segunda de mis hipótesis radica en que el sorteo es el único método de selección con una forma específica de humildad-legitimidad, mientras que los tres restantes modos de selección producen una superioridad-legitimidad que declara superior al representante por encima del representado a través del proceso de selección. How could we be thinking sortition efficiently? My proposal is to construct a general theory of sortition in a comparative approach. A broad study seems necessary in order to grasp the theoretical constants, despite the empirical diversity of sortition concrete uses. First, I shall compare sortition to the three other selection modes: election, nomination and certification. Second, I will analyse the deliberative frameworks, that is to say “who decides what how”. Third, I will distinguish four democratic principles of sortition: equality, impartiality, representativeness and legitimacy. My first research hypothesis is that sortition is likely to offer a greater equality, impartiality and representativeness. My second hypothesis is that sortition is the only method of selection producing a specific form, a humility-legitimacy when the three other selection modes are producing a superiority-legitimacy, where the principal is declared superior to the agent through the selection process.

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Vandamme, Pierre-Étienne, Vincent Jacquet, Christoph Niessen, John Pitseys, and Min Reuchamps. "Intercameral Relations in a Bicameral Elected and Sortition Legislature." Politics & Society 46, no. 3 (August 13, 2018): 381–400. http://dx.doi.org/10.1177/0032329218789890.

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The idea of a hybrid bicameral system combining election and sortition is investigated. More precisely, the article imagines how an elected and a sortition chamber would interact, taking into account their public perception and their competing legitimacies. The article draws on a survey of a representative sample of the Belgian population and Belgian members of parliament assessing their views about sortition in political representation. Findings are combined with theoretical reflections on election’s and sortition’s respective sources of legitimacy. The possibility of conflicting legitimacies and mutually detrimental interactions leads to considerations of the effects of different possible distributions of power between the chambers as a crucial determinant of their interactions and perceived legitimacy.

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13

Lv, Yuncheng, Jing Yang, Anbo Gao, Sha Sun, Xilong Zheng, Xi Chen, Wei Wan, et al. "Sortilin promotes macrophage cholesterol accumulation and aortic atherosclerosis through lysosomal degradation of ATP-binding cassette transporter A1 protein." Acta Biochimica et Biophysica Sinica 51, no. 5 (April 4, 2019): 471–83. http://dx.doi.org/10.1093/abbs/gmz029.

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Abstract Sortilin is closely associated with hyperlipidemia and the risk of atherosclerosis (AS). The role of sortilin and the underlying mechanism in peripheral macrophage are not fully understood. In this study, we investigated the effect of macrophage sortilin on ATP-binding cassette transporter A1 (ABCA1) expression, ABCA1-mediated cholesterol efflux, and aortic AS. Macrophage sortilin expression was upregulated by oxidized low-density lipoproteins (ox-LDLs) in both concentration- and time-dependent manners. Its expression reached the peak level when cells were incubated with 50 μg/ml ox-LDL for 24 h. Overexpression of sortilin in macrophage reduced cholesterol efflux, leading to an increase in intracellular total cholesterol, free cholesterol, and cholesterol ester. Sortilin was found to bind with ABCA1 protein and suppress macrophage ABCA1 expression, resulting in a decrease in cholesterol efflux from macrophages. The inhibitory effect of sortilin in cholesterol efflux was partially reversed by treatment with chloroquine, a lysosomal inhibitor. On the contrary, the ABCA1 protein level and ABCA1-mediated cholesterol efflux is increased by sortilin short hairpin RNA transfection. The fecal and biliary cholesterol 3H-sterol from cholesterol-laden mouse peritoneal macrophage was reduced by sortilin overexpression through lentivirus vector (LV)-sortilin in low-density lipoprotein receptor knockout mice, which was prevented by co-treatment with chloroquine. Treatment with LV-sortilin reduced plasma high-density lipoprotein and increased plasma ox-LDL levels. Accordingly, aortic lipid deposition and plaque area were exacerbated, and ABCA1 expression was reduced in mice in response to infection with LV-sortilin alone. These effects of LV-sortilin were partially reversed by chloroquine. Sortilin enhances lysosomal degradation of ABCA1 protein and suppresses ABCA1-mediated cholesterol efflux from macrophages, leading to foam cell formation and AS development.

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14

Botta, Roberta, Simonetta Lisi, Aldo Pinchera, Franco Giorgi, Claudio Marcocci, Anna Rita Taddei, Anna Maria Fausto, et al. "Sortilin Is a Putative Postendocytic Receptor of Thyroglobulin." Endocrinology 150, no. 1 (August 7, 2008): 509–18. http://dx.doi.org/10.1210/en.2008-0953.

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The Vps10p family member sortilin is involved in various cell processes, including protein trafficking. Here we found that sortilin is expressed in thyroid epithelial cells (thyrocytes) in a TSH-dependent manner, that the hormone precursor thyroglobulin (Tg) is a high-affinity sortilin ligand, and that binding to sortilin occurs after Tg endocytosis, resulting in Tg recycling. Sortilin was found to be expressed intracellularly in thyrocytes, as observed in mouse, human, and rat thyroid as well as in FRTL-5 cells. Sortilin expression was demonstrated to be TSH dependent, both in FRTL-5 cells and in mice treated with methimazole and perchlorate. Plasmon resonance binding assays showed that Tg binds to sortilin in a concentration-dependent manner and with high affinity, with Kd values that paralleled the hormone content of Tg. In addition, we found that Tg and sortilin interact in vivo and in cultured cells, as observed by immunoprecipitation, in mouse thyroid extracts and in COS-7 cells transiently cotransfected with sortilin and Tg. After incubation of FRTL-5 cells with exogenous, labeled Tg, sortilin and Tg interacted intracellularly, presumably within the endocytic pathway, as observed by immunofluorescence and immunoelectron microscopy, the latter technique showing some degree of Tg recycling. This was confirmed in FRTL-5 cells in which Tg recycling was reduced by silencing of the sortilin gene and in CHO cells transfected with sortilin in which recycling was increased. Our findings provide a novel pathway of Tg trafficking and a novel function of sortilin in the thyroid gland, the functional impact of which remains to be established. Evidence for a novel pathway of thyroglobulin trafficking and for a possible novel function of sortilin in the thyroid gland is discussed.

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Buttenschøn, Henriette Nørmølle, Marit Nielsen, Simon Glerup, and Ole Mors. "Investigation of serum levels of sortilin in response to antidepressant treatment." Acta Neuropsychiatrica 30, no. 2 (May 8, 2017): 111–16. http://dx.doi.org/10.1017/neu.2017.13.

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BackgroundThe identification of biomarkers for depression is of great clinical relevance as the diagnosis is currently subjective. Recent research points towards sortilin as a potential biomarker for depression, and the aim of the current study was to investigate the serum sortilin level in response to antidepressant treatment.MethodsThe study included 56 depressed individuals of which 41 responded to treatment. Depression scores and serum levels of sortilin were measured at baseline and after 12 weeks of antidepressant treatment. Statistical analyses were performed using Stata 13.ResultsThe depression score and response to treatment were not predicted by the sortilin level. Likewise, we observed no significant change in serum sortilin levels following 12 weeks of antidepressant treatment. Furthermore, no association between the serum sortilin level and depression score was observed.ConclusionThe results do not point towards sortilin as a state-dependent biomarker.

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Thaker, Adarsh M., and William H. Frishman. "Sortilin." Cardiology in Review 22, no. 2 (2014): 91–96. http://dx.doi.org/10.1097/crd.0000000000000008.

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Westerterp, Marit, and Alan R. Tall. "SORTILIN." Circulation Research 116, no. 5 (February 27, 2015): 764–66. http://dx.doi.org/10.1161/circresaha.115.306036.

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Sintomer, Yves. "From Deliberative to Radical Democracy? Sortition and Politics in the Twenty-First Century." Politics & Society 46, no. 3 (August 13, 2018): 337–57. http://dx.doi.org/10.1177/0032329218789888.

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This article defends four claims. The first is that in the last few decades, two waves of democratic innovation based on random selection must be differentiated by their partly different concrete devices, embodying different social dynamics and pointing toward different kinds of democracy. The second claim is that the rationale of the first wave, based on randomly selected minipublics, largely differs from the dynamic of political sortition in Athens, as it points toward deliberative democracy rather than radical democracy. Conversely, empowered sortition processes that have emerged during the second wave capture better the spirit of radical Athenian democratic traditions. The third claim is normative: these empowered sortition processes are more promising for a real democratization of democracy. The last claim is that any proposal of a legislature by lot must rely on this lesson when trying to defend a normatively convincing and politically realistic perspective.

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Northwood, S. J. "SORTITION IN THE REPUBLIC." Classical Review 52, no. 2 (September 2002): 314–16. http://dx.doi.org/10.1093/cr/52.2.314.

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Huang, Shanshan, Xingxing Yu, Haiqing Wang, and Jianlei Zheng. "Elevated serum sortilin is related to carotid plaque concomitant with calcification." Biomarkers in Medicine 14, no. 5 (April 2020): 381–89. http://dx.doi.org/10.2217/bmm-2019-0472.

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Aim: To explore whether elevated serum sortilin was associated with calcified carotid plaque and ischemic stroke. Methods: A total of 171 patients with cardiovascular risk factors were enrolled. Ultrasonography was performed to evaluate calcified plaques and noncalcified plaques. Serum sortilin concentration was measured by ELISA. Results: Serum sortilin level was higher in patients with calcified carotid plaque and positively related to carotid plaque burden, but not with ischemic stroke during the follow-up. Multivariable logistic regression analysis revealed serum sortilin level was an independent determinant for calcified carotid plaque (p = 0.001). Receiving operating characteristic analysis showed an area under the curve of sortilin for carotid calcification was 0.759. Conclusion: Higher serum sortilin level was associated with carotid calcification and severe carotid plaque score.

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Pan, Xiang, Nava Zaarur, Maneet Singh, Peter Morin, and Konstantin V. Kandror. "Sortilin and retromer mediate retrograde transport of Glut4 in 3T3-L1 adipocytes." Molecular Biology of the Cell 28, no. 12 (June 15, 2017): 1667–75. http://dx.doi.org/10.1091/mbc.e16-11-0777.

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Sortilin is a multiligand sorting receptor responsible for the anterograde transport of lysosomal enzymes and substrates. Here we demonstrate that sortilin is also involved in retrograde protein traffic. In cultured 3T3-L1 adipocytes, sortilin together with retromer rescues Glut4 from degradation in lysosomes and retrieves it to the TGN, where insulin-responsive vesicles are formed. Mechanistically, the luminal Vps10p domain of sortilin interacts with the first luminal loop of Glut4, and the cytoplasmic tail of sortilin binds to retromer. Ablation of the retromer does not affect insulin signaling but decreases the stability of sortilin and Glut4 and blocks their entry into the small vesicular carriers. As a result, Glut4 cannot reach the insulin-responsive compartment, and insulin-stimulated glucose uptake in adipocytes is suppressed. We suggest that sortilin- and retromer-mediated Glut4 retrieval from endosomes may represent a step in the Glut4 pathway vulnerable to the development of insulin resistance and diabetes.

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Andersen, Jacob Lauwring, Tenna Juul Schrøder, Søren Christensen, Dorthe Strandbygård, Lone Tjener Pallesen, Maria Marta García-Alai, Samsa Lindberg, et al. "Identification of the first small-molecule ligand of the neuronal receptor sortilin and structure determination of the receptor–ligand complex." Acta Crystallographica Section D Biological Crystallography 70, no. 2 (January 29, 2014): 451–60. http://dx.doi.org/10.1107/s1399004713030149.

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Sortilin is a type I membrane glycoprotein belonging to the vacuolar protein sorting 10 protein (Vps10p) family of sorting receptors and is most abundantly expressed in the central nervous system. Sortilin has emerged as a key player in the regulation of neuronal viability and has been implicated as a possible therapeutic target in a range of disorders. Here, the identification of AF40431, the first reported small-molecule ligand of sortilin, is reported. Crystals of the sortilin–AF40431 complex were obtained by co-crystallization and the structure of the complex was solved to 2.7 Å resolution. AF40431 is bound in the neurotensin-binding site of sortilin, with the leucine moiety of AF40431 mimicking the binding mode of the C-terminal leucine of neurotensin and the 4-methylumbelliferone moiety of AF40431 forming π-stacking with a phenylalanine.

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Stone, Peter. "The Political Potential of Sortition." Philosophical Quarterly 60, no. 240 (July 1, 2009): 664–66. http://dx.doi.org/10.1111/j.1467-9213.2010.660_11.x.

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Stone, Peter. "Sortition, voting, and democratic equality." Critical Review of International Social and Political Philosophy 19, no. 3 (March 10, 2016): 339–56. http://dx.doi.org/10.1080/13698230.2016.1144858.

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Larsen, Jakob Vejby, Maria Hansen, Bjarne Møller, Peder Madsen, Jürgen Scheller, Morten Nielsen, and Claus Munck Petersen. "Sortilin Facilitates Signaling of Ciliary Neurotrophic Factor and Related Helical Type 1 Cytokines Targeting the gp130/Leukemia Inhibitory Factor Receptor β Heterodimer." Molecular and Cellular Biology 30, no. 17 (June 28, 2010): 4175–87. http://dx.doi.org/10.1128/mcb.00274-10.

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ABSTRACT Sortilin is a member of the Vps10p domain family of neuropeptide and neurotrophin binding neuronal receptors. The family members interact with and partly share a variety of ligands and partake in intracellular sorting and protein transport as well as in transmembrane signal transduction. Thus, sortilin mediates the transport of both neurotensin and nerve growth factor and interacts with their respective receptors to facilitate ligand-induced signaling. Here we report that ciliary neurotrophic factor (CNTF), and related ligands targeting the established CNTF receptor α, binds to sortilin with high affinity. We find that sortilin may have at least two functions: one is to provide rapid endocytosis and the removal of CNTF, something which is not provided by CNTF receptor α, and the other is to facilitate CNTF signaling through the gp130/leukemia inhibitory factor (LIF) receptor β heterodimeric complex. Interestingly, the latter function is independent of both the CNTF receptor α and ligand binding to sortilin but appears to implicate a direct interaction with LIF receptor β. Thus, sortilin facilitates the signaling of all helical type 1 cytokines, which engage the gp130/LIF receptor β complex.

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Annabi, Borhane, Michel Demeule, Jean-Christophe Currie, Alain Larocque, Cyndia Charfi, and Richard Béliveau. "Increasing potency and safety of anticancer drugs through sortilin receptor-mediated cancer therapy: A new targeted approach for the treatment of ovarian cancer." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e17068-e17068. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e17068.

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e17068 Background: The development of personalized therapies against ovarian cancer remains highly challenging in current modern oncology. One strategy to achieve greater selectivity and better anticancer drug delivery into cancer cells is to conjugate cytotoxic agents to specific peptide ligands that selectively target receptors abundantly and/or exclusively expressed on these cells. Increased expression of Sortilin, a scavenging receptor, has been clinically observed in invasive ovarian cancer biopsies, and correlated with tumor grades. In light of this, we developed a peptide conjugation platform and a new Sortilin receptor-mediated vectorization strategy to increase cell targeting selectivity and cell delivery efficacy of anticancer agents. Methods: As a proof-of-concept, Doxorubicin was conjugated to a Sortilin binding peptide (KA-peptide). In vitro, intracellular delivery of the Doxorubicin-KA-peptide conjugate (DoxKA) was assessed in ES-2 and SKOV-3 ovarian cancer cell line models using flow cytometry and fluorescent microscopy. Sortilin gene silencing was performed with specific siRNA. DoxKA efficacy and safety were evaluated in vivo using ES-2 (CD1 nude mice) and SKOV-3 (athymic mice) subcutaneous xenograft models. Results: Uptake of DoxKA was observed in both Sortilin-positive ovarian cancer cell lines tested and was reduced when Sortilin expression was specifically silenced or upon competition with the Sortilin ligands Neurotensin and Progranulin. Results indicate that the uptake of DoxKA occurs via Sortilin-mediated endocytosis in contrast to simple diffusion for Doxorubicin. DoxKA was found to bypass the P-glycoprotein (P-gp) efflux pump in MDCK-MDR1 cells overexpressing P-gp as the uptake of DoxKA was unaffected by the P-gp inhibitor Cyclosporin A. In vivo, DoxKA showed lower potential side effects than Doxorubicin alone did, with decreased accumulation in healthy tissues such as heart and ovary. DoxKA caused a more potent inhibition of human ovarian tumor xenografts growth in mice and was better tolerated (absence of leukopenia and neutropenia) than the unconjugated Doxorubicin at an equivalent dose. Conclusions: These results strongly support the future clinical use of this platform to generate novel personalized therapeutics with specific targeting of Sortilin-positive tumors in the next stage of development in phase 1 clinical trial.

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Gastil, John, and Erik Olin Wright. "Preface to the Special Issue." Politics & Society 46, no. 3 (August 13, 2018): 299–301. http://dx.doi.org/10.1177/0032329218789882.

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Richner, M., O. J. Bjerrum, Y. De Koninck, A. Nykjaer, and C. B. Vaegter. "Sortilins in neuropathic pain." Scandinavian Journal of Pain 3, no. 3 (July 1, 2012): 183–84. http://dx.doi.org/10.1016/j.sjpain.2012.05.028.

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AbstractBackground/aimsThe molecular mechanisms underlying neuropathic pain are incompletely understood, but recent data suggest that down-regulation of the chloride extruding co-transporter KCC2 in spinal cord sensory neurons is critical: Following peripheral nerve injury, activated microglia in the spinal cord release BDNF, which stimulates neuronal TrkB receptors and ultimately results in the reduction of KCC2 levels. Consequently, neuronal intracellular chloride ion concentration increases, impairing GABAA-receptor mediated inhibition. We have previously described how the receptor sortilin modulates neurotrophin signaling by facilitating anterograde transport of Trk receptors. Unpublished data further link SorCS2, another member of the Sortilins family of sorting receptors (sortilin, SorLA and SorCS1–3) to BDNF signaling by regulating presynaptic TrkB trafficking. The purpose of this study is to explore the involvement of Sortilins in neuropathic pain.MethodsWe subjected wild-type (wt), sortilin knockout (Sort1-/-) and SorCS2 knockout (SorCS2-/-) mice to the Spared Nerve Injury (SNI) model of peripheral nerve injury. Mechanical allodynia was measured by von Frey filaments using the up-down-up method and a 3-out-of-5 thresshold.ResultsAs previously described by several groups, wt mice developed significant mechanical allodynia following SNI. Interestingly however, mice lacking sortilin or SorCS2 were fully protected from development of allodynia and did not display KCC2 down-regulation following injury. In addition, a single intrathecal injection of antibodies against sortilin or SorCS2 could delay or rescue mechanical allodynia in wt SNI mice for 2-3 days. Finally, neither sortilin nor SorCS2 deficient mice responded to intrathecal injection of BDNF, in contrast to wt mice which developed transient mechanical allodynia.ConclusionWe hypothesize that sortilin and SorCS2 are involved in neuropathic pain development by regulating TrkB signaling. Alternatively, Sortilins may directly influence the regulation of KCC2 membrane levels following injury. Both hypotheses are currently being investigated by our group.

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Vukolova, Yu Yu, and I. V. Gubareva. "Relationship of sortilin and proprotein convertase subtilisin/kexin type 9 in blood serum with the severity of carotid and coronary atherosclerosis in hypertensive patients." Russian Journal of Cardiology 27, no. 2S (April 30, 2022): 4903. http://dx.doi.org/10.15829/1560-4071-2022-4903.

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Sortilin is an important molecular protein involved in lipid metabolism, atherosclerosis, and aortic valve calcification. Sortilin presumably regulates the PCSK9 signaling pathways.Aim. To study correlations of sortilin and PCSK9 with atherosclerosis development in hypertensive patients.Material and methods. The study included 161 patients aged 30 to 65 years. We performed collection of complaints and anamnesis, physical examination, blood biochemical test with the determination of total cholesterol, low-density lipoprotein cholesterol, triglycerides, blood glucose, serum creatinine with estimation of glomerular filtration rate. Serum PCSK9, sortilin and interleukins 8, 10 were determined by enzyme-linked immunosorbent assay. The following investigations were also performed: electrocardiography, echocardiography, extracranial artery ultrasound, coronary angiography.Results. Sortilin levels (b=2,37; odds ratio (OR), 10,74; 95% CI, 1,05-109,47, p=0,045), IL-8 (b=-2,42; OR, 9,74; 95% CI, 0,01-0,81, p=0,032), age (b=0,21; OR, 1,24; 95% CI, 1,12-1,37, p<0,001) were identified as independent predictors of coronary atherosclerosis with a sensitivity of 87% and a specificity of 70%. PCSK9 (b=0,005; OR, 1,00; 95% CI, 1,00-1,01, p=0,038) and IL-8 (b= -0,33; OR, 0,72; 95% CI, 0,55-0,94, p=0,014) were identified as independent predictors of carotid atherosclerosis with a sensitivity of 75% and a specificity of 71%.Conclusion. In addition to non-invasive imaging, the determination of atherosclerosis biomarkers can make a significant contribution to the diagnosis and prediction of carotid and coronary atherosclerosis progression. It is noteworthy that not only PCSK9, but also sortilin can be a potential therapeutic target. Further large-scale studies are needed.

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Dedoni, Simona, Luisa Marras, Maria C. Olianas, Angela Ingianni, and Pierluigi Onali. "Valproic acid upregulates the expression of the p75NTR/sortilin receptor complex to induce neuronal apoptosis." Apoptosis 25, no. 9-10 (July 25, 2020): 697–714. http://dx.doi.org/10.1007/s10495-020-01626-0.

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Abstract The antiepileptic and mood stabilizer agent valproic acid (VPA) has been shown to exert anti-tumour effects and to cause neuronal damage in the developing brain through mechanisms not completely understood. In the present study we show that prolonged exposure of SH-SY5Y and LAN-1 human neuroblastoma cells to clinically relevant concentrations of VPA caused a marked induction of the protein and transcript levels of the common neurotrophin receptor p75NTR and its co-receptor sortilin, two promoters of apoptotic cell death in response to proneurotrophins. VPA induction of p75NTR and sortilin was associated with an increase in plasma membrane expression of the receptor proteins and was mimicked by cell treatment with several histone deacetylase (HDAC) inhibitors. VPA and HDAC1 knockdown decreased the level of EZH2, a core component of the polycomb repressive complex 2, and upregulated the transcription factor CASZ1, a positive regulator of p75NTR. CASZ1 knockdown attenuated VPA-induced p75NTR overexpression. Cell treatment with VPA favoured proNGF-induced p75NTR/sortilin interaction and the exposure to proNGF enhanced JNK activation and apoptotic cell death elicited by VPA. Depletion of p75NTR or addition of the sortilin agonist neurotensin to block proNGF/sortilin interaction reduced the apoptotic response to VPA and proNGF. Exposure of mouse cerebellar granule cells to VPA upregulated p75NTR and sortilin and induced apoptosis which was enhanced by proNGF. These results indicate that VPA upregulates p75NTR apoptotic cell signalling through an epigenetic mechanism involving HDAC inhibition and suggest that this effect may contribute to the anti-neuroblastoma and neurotoxic effects of VPA.

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Malleson, Tom. "Should Democracy Work through Elections or Sortition?" Politics & Society 46, no. 3 (August 13, 2018): 401–17. http://dx.doi.org/10.1177/0032329218789891.

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Are democratic ideals better served by elections or sortition? Is the ideal national legislature one that is elected, chosen by lot, or some combination thereof? To answer these questions properly, it is necessary to perform a careful, balanced, and systematic comparison of the strengths and weaknesses of each. To do so, this article uses foundational democratic values—political equality, popular control, deliberative nature, and competency—as measuring sticks. On the basis of these values a purely elected legislature is compared with a purely sortition one, on the assumption that each has the full decision-making powers normally possessed by national legislatures. This big picture will provide a clearer view of the strengths and weaknesses of the respective systems and their trade-offs, as well as the open questions that remain.

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Saran, Rene, and Norovsambuu Tumennasan. "Whose opinion counts? Implementation by sortition." Games and Economic Behavior 78 (March 2013): 72–84. http://dx.doi.org/10.1016/j.geb.2012.12.001.

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Pan, Xiang, Anatoli Meriin, Guanrong Huang, and Konstantin V. Kandror. "Insulin-responsive amino peptidase follows the Glut4 pathway but is dispensable for the formation and translocation of insulin-responsive vesicles." Molecular Biology of the Cell 30, no. 12 (June 2019): 1536–43. http://dx.doi.org/10.1091/mbc.e18-12-0792.

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In fat and skeletal muscle cells, insulin-responsive amino peptidase (IRAP) along with glucose transporter 4 (Glut4) and sortilin, represents a major component protein of the insulin-responsive vesicles (IRVs). Here, we show that IRAP, similar to Glut4 and sortilin, is retrieved from endosomes to the trans-Golgi network by retromer. Unlike Glut4, retrograde transport of IRAP does not require sortilin, as retromer can directly bind to the cytoplasmic tail of IRAP. Ablation of IRAP in 3T3-L1 adipocytes shifts the endosomal pool of Glut4 to more acidic endosomes, but does not affect IRV targeting, stability, and insulin responsiveness of Glut4.

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Tall, Alan R., and Ding Ai. "Sorting Out Sortilin." Circulation Research 108, no. 2 (January 21, 2011): 158–60. http://dx.doi.org/10.1161/res.0b013e31820d7daa.

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Mortensen, Martin B., Mads Kjolby, and Jacob F. Bentzon. "Sortilin and atherosclerosis." Oncotarget 6, no. 23 (August 4, 2015): 19352–53. http://dx.doi.org/10.18632/oncotarget.5098.

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Fulmer, Tim. "Sorting out sortilin." Science-Business eXchange 3, no. 32 (August 2010): 973. http://dx.doi.org/10.1038/scibx.2010.973.

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Avvisato, Roberta, Stanislovas S. Jankauskas, Fahimeh Varzideh, Urna Kansakar, Pasquale Mone, and Gaetano Santulli. "Sortilin and hypertension." Current Opinion in Nephrology & Hypertension 32, no. 2 (December 23, 2022): 134–40. http://dx.doi.org/10.1097/mnh.0000000000000866.

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Gumina, Valentina, Elisa Onesto, Claudia Colombrita, AnnaMaria Maraschi, Vincenzo Silani, and Antonia Ratti. "Inter-Species Differences in Regulation of the Progranulin–Sortilin Axis in TDP-43 Cell Models of Neurodegeneration." International Journal of Molecular Sciences 20, no. 23 (November 22, 2019): 5866. http://dx.doi.org/10.3390/ijms20235866.

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Cytoplasmic aggregates and nuclear depletion of the ubiquitous RNA-binding protein TDP-43 have been described in the autoptic brain tissues of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTLD) patients and both TDP-43 loss-of-function and gain-of-function mechanisms seem to contribute to the neurodegenerative process. Among the wide array of RNA targets, TDP-43 regulates progranulin (GRN) mRNA stability and sortilin (SORT1) splicing. Progranulin is a secreted neurotrophic and neuro-immunomodulatory factor whose endocytosis and delivery to the lysosomes are regulated by the neuronal receptor sortilin. Moreover, GRN loss-of-function mutations are causative of a subset of FTLD cases showing TDP-43 pathological aggregates. Here we show that TDP-43 loss-of-function differently affects the progranulin–sortilin axis in murine and human neuronal cell models. We demonstrated that although TDP-43 binding to GRN mRNA occurs similarly in human and murine cells, upon TDP-43 depletion, a different control of sortilin splicing and protein content may determine changes in extracellular progranulin uptake that account for increased or unchanged secreted protein in murine and human cells, respectively. As targeting the progranulin–sortilin axis has been proposed as a therapeutic approach for GRN-FTLD patients, the inter-species differences in TDP-43-mediated regulation of this pathway must be considered when translating studies from animal models to patients.

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Nosrati Andevari, Ali, Soheila Moein, Durdi Qujeq, Zoleikha Moazezi, and Karimollah Hajian Tilaki. "Effects of atrovastatin on concentrations of 3-hydroxy-3-methylglutaryl-coenzyme A- reductase (HMG-CoA-R), proprotein convertase subtilisin/kexin type 9 (PCSK9) and sortilin in patients with type 2 diabetes mellitus and pre-diabetics." Journal of Nephropathology 10, no. 1 (July 2, 2020): e05-e05. http://dx.doi.org/10.34172/jnp.2021.05.

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Introduction: Atorvastatin hinders cardiovascular disease by reducing cholesterol levels. Proprotein convertase subtilisin/kexin type 9 (PCSK9) enhances the secretion of insulin by binding to LDL receptor. Sortilin is committed in the transfer of intracellular proteins through the plasma membrane. Objectives: The purpose of this research was to determine the effect of atorvastatin consumption on alterations in the levels of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA-R), PCSK9 and sortilin in diabetic patients and pre-diabetics. Patients and Methods: This study was carried out on 80 individuals including normal subjects, diabetic patients and pre-diabetics. The participated individuals were divided as control group (i) (healthy individuals without diabetes mellitus), diabetic group receiving statin (ii), diabetic group not receiving statin (iii), pre-diabetic group receiving statin (iv) and pre-diabetic group not receiving statin (v). Levels of HMG-COA-R, PCSK9 and sortilin were determined by ELISA method. Results: In diabetics and pre-diabetics taking atorvastatin, the level of HMG-COA-R was not altered significantly compared to diabetics and pre-diabetics not taking atorvastatin, respectively (P> 0.05). The serum PCSK9 level in diabetics and pre-diabetics was significantly higher than the healthy individuals (P= 0.001). Additionally, the serum PCSK9 level in diabetics and pre-diabetics receiving atorvastatin was significantly higher than diabetics and pre-diabetics not receiving atorvastatin, respectively (P=0.001). The serum sortilin level in diabetics and pre-diabetics was significantly higher than the healthy individuals (P=0.001). In addition, the serum sortilin level in pre-diabetics receiving atorvastatin was significantly higher than pre-diabetics not receiving atorvastatin (P=0.001). Conclusion: Atorvastatin improved insulin secretion and sensitivity by increasing serum sortilin and PCSK9 levels. Thereby, it prevented the development of diabetes in diabetics and the progression of pre-diabetes to diabetes in pre-diabetics.

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Venkat, Swati, and Adam D. Linstedt. "Manganese-induced trafficking and turnover of GPP130 is mediated by sortilin." Molecular Biology of the Cell 28, no. 19 (September 15, 2017): 2569–78. http://dx.doi.org/10.1091/mbc.e17-05-0326.

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Elevated, nontoxic doses of manganese (Mn) protect against Shiga toxin-1–induced cell death via down-regulation of GPP130, a cycling Golgi membrane protein that serves as an endosome-to-Golgi trafficking receptor for the toxin. Mn binds to GPP130 in the Golgi and causes GPP130 to oligomerize/aggregate, and the complexes are diverted to lysosomes. In fact, based on experiments using the self-interacting FM domain, it appears generally true that aggregation of a Golgi protein leads to its lysosomal degradation. How such oligomers are selectively sorted out of the Golgi is unknown. Here we provide evidence that Mn-induced exit of GPP130 from the trans-Golgi network (TGN) toward lysosomes is mediated by the sorting receptor sortilin interacting with the lumenal stem domain of GPP130. In contrast, FM-induced lysosomal trafficking of the Golgi protein galactosyltransferase was sortilin independent and occurred even in the absence of its native lumenal domain. Thus sortilin-dependent as well as sortilin-independent sorting mechanisms target aggregated Golgi membrane proteins for lysosomal degradation.

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Drew, Joseph. "Can local government by lottery increase democratic responsiveness?" Policy & Politics 47, no. 4 (October 1, 2019): 621–36. http://dx.doi.org/10.1332/030557319x15653392161339.

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In recent years, scholars have paid significant attention to the role of decentralisation in restraining government power and budgetary excess. Yet growth in taxation and debt in OECD countries suggests that such measures have often had a limited effect in taming ‘local Leviathans’. In response, this Research Provocation sets out a bold alternative vision, advocating the use of sortition ‐ the deliberate introduction of arationality and chance into local policy decisions ‐ in order to disrupt ingrained power imbalances and enhance democratic participation. It argues that sortition has the potential to provide for greater possibilities for citizens to exercise voice, choice and exit. This in turn, it is argued, can ensure that local government is more responsive to the preferences of ordinary citizens. In making this provocative argument, we offer an important contribution to debates regarding citizen disengagement, democratic malaise and the potential of more deliberative forms of democracy to address such challenges.

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Yang, Miao, Yoon Lim, Xiaojiang Li, Jin-Hua Zhong, and Xin-Fu Zhou. "Precursor of Brain-derived Neurotrophic Factor (proBDNF) Forms a Complex with Huntingtin-associated Protein-1 (HAP1) and Sortilin That Modulates proBDNF Trafficking, Degradation, and Processing." Journal of Biological Chemistry 286, no. 18 (February 28, 2011): 16272–84. http://dx.doi.org/10.1074/jbc.m110.195347.

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proBDNF, a precursor of brain-derived neurotrophic factor (BDNF), is anterogradely transported and released from nerve terminals, but the mechanism underlying this process remains unclear. In this study, we report that proBDNF forms a complex with Huntingtin associated protein-1 (HAP1) and sortilin, which plays an important role in proBDNF intracellular trafficking and stabilization. The interaction of proBDNF with both HAP1A and sortilin in co-transfected HEK293 cells is confirmed by both fluorescence resonance energy transfer and co-immunoprecipitation. The frequent co-localization (>90%) of endogenous HAP1, sortilin, and proBDNF is also found in cultured cortical neurons. Mapping studies using GST pulldown and competition assays has defined the interacting region of HAP1 with proBDNF within amino acids 371–445 and the binding sequences of proBDNF to HAP1 between amino acids 65 and 90. Fluorescence recovery after photobleaching confirms the defective movement of proBDNF-containing vesicles in neurites of HAP1−/− neurons, which can be partially restored by reintroducing HAP1 cDNA into the neurons. However, the effect is significantly increased by simultaneously reintroducing both HAP1 and sortilin. proBDNF and HAP1 are highly co-localized with organelle markers for the Golgi network, microtubules, molecular motor, or endosomes in normal neurons, but this co-localization is reduced in HAP1−/− neurons. Co-immunoprecipitation and Western blot showed that sortilin stabilizes the proBDNF·HAP1 complex in co-transfected HEK293 cells, helping to prevent proBDNF degradation. Furthermore, the complex facilitates furin cleavage to release mature BDNF.

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Mazella, Jean. "Deciphering Mechanisms of Action of Sortilin/Neurotensin Receptor-3 in the Proliferation Regulation of Colorectal and Other Cancers." International Journal of Molecular Sciences 23, no. 19 (October 6, 2022): 11888. http://dx.doi.org/10.3390/ijms231911888.

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The purpose of this review is to decipher the mechanisms of the pathways leading to the complex roles of neurotensin (NTS) receptor-3, also called sortilin, and of its soluble counterpart (sSortilin/NTSR3) in a large amount of physiological and pathological functions, particularly in cancer progression and metastasis. Sortilin/NTSR3 belongs to the family of type I transmembrane proteins that can be shed to release its extracellular domain from all the cells expressing the protein. Since its discovery, extensive investigations into the role of both forms of Sortilin/NTSR3 (membrane-bound and soluble form) have demonstrated their involvement in many pathophysiological processes from cancer development to cardiovascular diseases, Alzheimer’s disease, diabetes, and major depression. This review focuses particularly on the implication of membrane-bound and soluble Sortilin/NTSR3 in colorectal cancer tissues and cells depending on its ability to be associated either to neurotrophins (NTs) or to NTS receptors, as well as to other cellular components such as integrins. At the end of the review, some hypotheses are suggested to counteract the deleterious effects of these proteins in order to develop effective anti-cancer treatments.

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Wu, Yaqin, Pengxin Song, and Fuxin Wang. "Hybrid Consensus Algorithm Optimization: A Mathematical Method Based on POS and PBFT and Its Application in Blockchain." Mathematical Problems in Engineering 2020 (April 13, 2020): 1–13. http://dx.doi.org/10.1155/2020/7270624.

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Blockchain is a new technology for processing complex and disordered information with respect to business and other industrial applications. This work is aimed at studying the consensus algorithm of blockchain to improve the performance of blockchain. Despite their advantages, the proof of stake (POS) algorithm and the practical Byzantine fault tolerance (PBFT) algorithm have high latency, low throughput, and poor scalability. In this paper, a blockchain hybrid consensus algorithm which combines advantages of the POS and PBFT algorithms is proposed, and the algorithm is divided into two stages: sortition and witness. The proposed algorithm reduces the number of consensus nodes to a constant value by verifiable pseudorandom sortition and performs transaction witness between nodes. The algorithm is improved and optimized from three dimensions: throughput, latency, and scalability. The experimental results show that the improved hybrid consensus algorithm is significantly superior to the previous single algorithms for its excellent scalability, high throughput, and low latency.

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Patel, Arti B., Irene Tsilioni, Susan E. Leeman, and Theoharis C. Theoharides. "Neurotensin stimulates sortilin and mTOR in human microglia inhibitable by methoxyluteolin, a potential therapeutic target for autism." Proceedings of the National Academy of Sciences 113, no. 45 (September 23, 2016): E7049—E7058. http://dx.doi.org/10.1073/pnas.1604992113.

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We had reported elevated serum levels of the peptide neurotensin (NT) in children with autism spectrum disorders (ASD). Here, we show that NT stimulates primary human microglia, the resident immune cells of the brain, and the immortalized cell line of human microglia-SV40. NT (10 nM) increases the gene expression and release (P < 0.001) of the proinflammatory cytokine IL-1β and chemokine (C-X-C motif) ligand 8 (CXCL8), chemokine (C-C motif) ligand 2 (CCL2), and CCL5 from human microglia. NT also stimulates proliferation (P < 0.05) of microglia-SV40. Microglia express only the receptor 3 (NTR3)/sortilin and not the NTR1 or NTR2. The use of siRNA to target sortilin reduces (P < 0.001) the NT-stimulated cytokine and chemokine gene expression and release from human microglia. Stimulation with NT (10 nM) increases the gene expression of sortilin (P < 0.0001) and causes the receptor to be translocated from the cytoplasm to the cell surface, and to be secreted extracellularly. Our findings also show increased levels of sortilin (P < 0.0001) in the serum from children with ASD (n = 36), compared with healthy controls (n = 20). NT stimulation of microglia-SV40 causes activation of the mammalian target of rapamycin (mTOR) signaling kinase, as shown by phosphorylation of its substrates and inhibition of these responses by drugs that prevent mTOR activation. NT-stimulated responses are inhibited by the flavonoid methoxyluteolin (0.1–1 μM). The data provide a link between sortilin and the pathological findings of microglia and inflammation of the brain in ASD. Thus, inhibition of this pathway using methoxyluteolin could provide an effective treatment of ASD.

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Lui, Ashley, Robert Sparks, Rekha Patel, and Niketa A. Patel. "Identification of Sortilin Alternatively Spliced Variants in Mouse 3T3L1 Adipocytes." International Journal of Molecular Sciences 22, no. 3 (January 20, 2021): 983. http://dx.doi.org/10.3390/ijms22030983.

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Type 2 diabetes mellitus is a metabolic disorder defined by systemic insulin resistance. Insulin resistance in adipocytes, an important regulator of glucose metabolism, results in impaired glucose uptake. The trafficking protein, sortilin, regulates major glucose transporter 4 (Glut4) movement, thereby promoting glucose uptake in adipocytes. Here, we demonstrate the presence of an alternatively spliced sortilin variant (Sort17b), whose levels increase with insulin resistance in mouse 3T3L1 adipocytes. Using a splicing minigene, we show that inclusion of alternative exon 17b results in the expression of Sort17b splice variant. Bioinformatic analysis indicated a novel intrinsic disorder region (IDR) encoded by exon 17b of Sort17b. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) measurements using molecular dynamics demonstrated increased flexibility of the protein backbone within the IDR. Using protein–protein docking and co-immunoprecipitation assays, we show robust binding of Glut4 to Sort17b. Further, results demonstrate that over-expression of Sort17b correlates with reduced Glut4 translocation and decreased glucose uptake in adipocytes. The study demonstrates that insulin resistance in 3T3L1 adipocytes promotes expression of a novel sortilin splice variant with thus far unknown implications in glucose metabolism. This knowledge may be used to develop therapeutics targeting sortilin variants in the management of type 2 diabetes and metabolic syndrome.

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Richner, Mette, Lone T. Pallesen, Maj Ulrichsen, Ebbe T. Poulsen, Thomas H. Holm, Hande Login, Annie Castonguay, et al. "Sortilin gates neurotensin and BDNF signaling to control peripheral neuropathic pain." Science Advances 5, no. 6 (June 2019): eaav9946. http://dx.doi.org/10.1126/sciadv.aav9946.

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Neuropathic pain is a major incurable clinical problem resulting from peripheral nerve trauma or disease. A central mechanism is the reduced expression of the potassium chloride cotransporter 2 (KCC2) in dorsal horn neurons induced by brain-derived neurotrophic factor (BDNF), causing neuronal disinhibition within spinal nociceptive pathways. Here, we demonstrate how neurotensin receptor 2 (NTSR2) signaling impairs BDNF-induced spinal KCC2 down-regulation, showing how these two pathways converge to control the abnormal sensory response following peripheral nerve injury. We establish how sortilin regulates this convergence by scavenging neurotensin from binding to NTSR2, thus modulating its inhibitory effect on BDNF-mediated mechanical allodynia. Using sortilin-deficient mice or receptor inhibition by antibodies or a small-molecule antagonist, we lastly demonstrate that we are able to fully block BDNF-induced pain and alleviate injury-induced neuropathic pain, validating sortilin as a clinically relevant target.

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Strong, Alanna, Kevin Patel, and Daniel J. Rader. "Sortilin and lipoprotein metabolism." Current Opinion in Lipidology 25, no. 5 (October 2014): 350–57. http://dx.doi.org/10.1097/mol.0000000000000110.

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Gubareva, I. V., and Y. Y. Vukolova. "Sortilin as a marker of atherosclerosis: biological and pathophysiological aspects." "Arterial’naya Gipertenziya" ("Arterial Hypertension") 27, no. 4 (October 20, 2021): 402–8. http://dx.doi.org/10.18705/1607-419x-2021-27-4-402-408.

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Subclinical atherosclerosis is an independent predictor of increased cardiovascular risk, including patients with hypertension. The article provides an overview of the pathogenetic role in atherogenesis and cardiovascular risk stratification of sortilin peptide which belongs to the family of vacuolar sorting receptors of type I. Circulating sortilin impacts both lipid and non-lipid pathogenetic mechanisms of atherogenesis. It can serve as an early biomarker of cardiovascular risk and a potential therapeutic target for dyslipidemia management and atherosclerosis at subclinical level.

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Barnes, Jarrod W., Megan Aarnio-Peterson, Joy Norris, Mark Haskins, Heather Flanagan-Steet, and Richard Steet. "Upregulation of Sortilin, a Lysosomal Sorting Receptor, Corresponds with Reduced Bioavailability of Latent TGFβ in Mucolipidosis II Cells." Biomolecules 10, no. 5 (April 26, 2020): 670. http://dx.doi.org/10.3390/biom10050670.

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Mucolipidosis II (ML-II) is a lysosomal disease caused by defects in the carbohydrate-dependent sorting of soluble hydrolases to lysosomes. Altered growth factor signaling has been identified as a contributor to the phenotypes associated with ML-II and other lysosomal disorders but an understanding of how these signaling pathways are affected is still emerging. Here, we investigated transforming growth factor beta 1 (TGFβ1) signaling in the context of ML-II patient fibroblasts, observing decreased TGFβ1 signaling that was accompanied by impaired TGFβ1-dependent wound closure. We found increased intracellular latent TGFβ1 complexes, caused by reduced secretion and stable localization in detergent-resistant lysosomes. Sortilin, a sorting receptor for hydrolases and TGFβ-related cytokines, was upregulated in ML-II fibroblasts as well as GNPTAB-null HeLa cells, suggesting a mechanism for inappropriate lysosomal targeting of TGFβ. Co-expression of sortilin and TGFβ in HeLa cells resulted in reduced TGFβ1 secretion. Elevated sortilin levels correlated with normal levels of cathepsin D in ML-II cells, consistent with a compensatory role for this receptor in lysosomal hydrolase targeting. Collectively, these data support a model whereby sortilin upregulation in cells with lysosomal storage maintains hydrolase sorting but suppresses TGFβ1 secretion through increased lysosomal delivery. These findings highlight an unexpected link between impaired lysosomal sorting and altered growth factor bioavailability.

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Journal articles on the topic 'Sortitio'

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