Neuroprotection mediated by cystatin C-loaded extracellular vesicles

Scientific Reports
Rocío Pérez-GonzálezEfrat Levy

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 ...Continue Reading

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Citations

Jan 9, 2020·Frontiers in Neuroscience·Paul M Mathews, Efrat Levy
May 23, 2020·Scientific Reports·Joana Maria Ramis
Mar 18, 2021·Ageing Research Reviews·Tongmei ZhangYouming Lu
Jul 11, 2021·Neurochemical Research·Qwynn LandfieldMariko Saito

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Methods Mentioned

BETA
Protein Assay
electrophoresis
FCS

Software Mentioned

Advantage CCD Camera System

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