Regional deficiencies in chaperone-mediated autophagy underlie α-synuclein aggregation and neurodegeneration.

ABSTRACT: In neurodegenerative diseases, it remains unclear why certain brain regions are selectively vulnerable to protein aggregation. In transgenic mice expressing human A53T α-synuclein, the brainstem and spinal cord develop the most prominent α-synuclein inclusions which correlate with age-dependent motor dysfunction. Herein we present the novel finding that this selective aggregation is in part dependent on the inability of chaperone-mediated autophagy (CMA) to effectively degrade α-synuclein in these brain regions. Lysosomal assays revealed that CMA activity was significantly decreased in aggregation-prone regions compared to the remainder of the brain. Previously, CMA activity has been shown to be proportional to levels of the CMA receptor Lamp-2a. Using antibodies, brain tissue from Lamp-2a

SUBMITTER: Malkus KA 

PROVIDER: S-EPMC3352979 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature