Neuroprotection mediated by cystatin C-loaded extracellular vesicles
Pérez-González, Rocío (Institut d'Investigació Biomèdica Sant Pau)
Sahoo, Susmita (Icahn School of Medicine at Mount Sinai)
Gauthier, Sebastien A. (Nathan S. Kline Institute)
Kim, Yohan (NYU Langone Medical Center)
Li, Meihua (Nathan S. Kline Institute)
Kumar, Asok (Nathan S. Kline Institute)
Pawlik, Monika (Nathan S. Kline Institute)
Benussi, Luisa (IRCCS Istituto Centro San Giovanni di Dio-Fatebenefratelli)
Ghidoni, Roberta (IRCCS Istituto Centro San Giovanni di Dio-Fatebenefratelli)
Levy, Efrat (Neuroscience Institute)
Universitat Autònoma de Barcelona

Date:	2019
Abstract:	Cystatin C (CysC) is implicated in neuroprotection and repair in the nervous system in response to diverse neurotoxic conditions. In addition to being secreted from cells in a soluble form, CysC is released by cells in association with extracellular vesicles (EVs), including exosomes. We demonstrate that EVs containing CysC protect cultured cells from starvation-induced death. Moreover, while EVs secreted by CysC-deficient cells were not protective, EVs secreted by CysC-deficient cells treated with exogenous human CysC significantly enhanced the survival of the cells. CysC also plays a role in modulating the secretion of EVs, enhancing secretion of EVs by primary cortical neurons and primary cortical smooth muscle cells. Confirming these in vitro findings, higher EV levels were observed in the brain extracellular space of transgenic mice expressing human CysC as compared to littermate controls. Regulation of cell-secreted EV levels and content in the brain is likely to be essential to maintaining normal brain function. We propose that enhanced EV release could rescue the deleterious effects of dysfunction of the endosomal-lysosomal system in neurodegenerative disorders. Moreover, a higher level of CysC-loaded EVs released from cells in the central nervous system has important protective functions, representing a potential therapeutic tool for disorders of the central nervous system.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Exocytosis ; Stress and resilience
Published in:	Scientific reports, Vol. 9 Núm. 1 (31 2019) , p. 11104, ISSN 2045-2322

DOI: 10.1038/s41598-019-47524-7
PMID: 31367000

10 p, 1.6 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles