A new perspective in Parkinson's disease, chaperone-mediated autophagy

Parkinson's disease (PD) is an age-related neurodegenerative disease characterized by loss of dopaminergic neurons and aggregation of alpha-synuclein. Although the role of alpha-synuclein in the pathology of PD is still unclear, the fact that its aggregation contributes to the loss of dopaminergic neurons has been confirmed. Therefore, controlling the alpha-synuclein protein level may be critical for PD pathogenesis and may provide potential therapeutics. Wild-type alpha-synuclein is physiologically degraded by chaperone-mediated autophagy (CMA), and dysfunction of CMA results in alpha-synuclein aggregation and compensative macroautophagy activation which finally leads to cell death. Therefore, CMA may participate in PD pathogenesis as a very important factor, and up-regulating CMA activity could degrade overloaded alpha-synuclein. In view of potential compensative effects, maintenance of the balance of CMA activity will be another major challenge in the future development of the therapeutic strategy. Herein we review the current knowledge of the role of CMA in PD. (C) 2010 Elsevier Ltd. All rights reserved.