LAMP2A as a therapeutic target in Parkinson disease.

Abstract:

:Abnormal aggregation of SNCA/?-synuclein plays a crucial role in Parkinson disease (PD) pathogenesis. SNCA levels determine its toxicity, and its accumulation, even to a small extent, may be a risk factor for neurodegeneration. One of the main pathways for SNCA degradation is chaperone-mediated autophagy (CMA), a selective form of autophagy, while aberrant SNCA may act as a CMA inhibitor. In the current punctum we summarize our recent data showing that induction of CMA, via overexpression of the protein controlling its rate-limiting step, the lysosomal receptor LAMP2A, effectively decreases SNCA levels and ameliorates SNCA-induced neurodegeneration, both in neuronal cell culture systems and in the rat brain. Such findings suggest that modulation of LAMP2A and, consequently, CMA, represents a viable therapeutic target for PD and other synucleinopathies where SNCA accumulation and aggregation plays a fundamental role.

journal_name

Autophagy

journal_title

Autophagy

authors

Xilouri M,Brekk OR,Kirik D,Stefanis L

doi

10.4161/auto.26451

subject

Has Abstract

pub_date

2013-12-01 00:00:00

pages

2166-8

issue

12

eissn

1554-8627

issn

1554-8635

pii

26451

journal_volume

9

pub_type

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