alexa Chaperone-mediated autophagy dysfunction in the pathogenesis of neurodegeneration.


Journal of Medical & Surgical Pathology

Author(s): Koga H, Cuervo AM

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Abstract Chaperone-mediated autophagy (CMA) contributes to selective degradation of individual soluble proteins in lysosomes. Unique to this type of autophagy is the fact that proteins reach the lysosomal lumen for degradation by directly crossing the lysosomal membrane, in contrast with the vesicle-mediated delivery characteristic of the other types of autophagy. These two characteristics--selective targeting and direct translocation of substrates--determine the contribution of CMA to different physiological functions and the type of pathological conditions associated with CMA dysfunction. In this review, we briefly revise recent findings on the molecular mechanisms behind CMA function, and describe the physiological relevance of the selective lysosomal degradation through this pathway. We also comment on the cellular consequences of CMA malfunction and on the connections already established between CMA dysfunction and different human disorders, with special emphasis on neurodegenerative diseases. This article is part of a Special Issue entitled "Autophagy and protein degradation in neurological diseases." Copyright © 2010 Elsevier Inc. All rights reserved.
This article was published in Neurobiol Dis and referenced in Journal of Medical & Surgical Pathology

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