The Parkinson disease protein α-synuclein inhibits autophagy - PubMed (original) (raw)

Review

The Parkinson disease protein α-synuclein inhibits autophagy

Ashley R Winslow et al. Autophagy. 2011 Apr.

Abstract

Parkinson disease (PD) is the most common movement disorder affecting people. It is characterized by the accumulation of the protein α-synuclein in Lewy body inclusions in vulnerable neurons. α-Synuclein overexpression caused by gene multiplications is sufficient to cause this disease, suggesting that α-synuclein accumulation is toxic. Here we review our recent study showing that α-synuclein inhibits autophagy. We discuss our mechanistic understanding of this phenomenon and also speculate how a deficiency in autophagy may contribute to a range of pleiotropic features of PD biology.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Autophagy inhibition by alpha-synuclein may contribute to Parkinson disease pathogenesis. In normal, healthy cells, Atg9 colocalizes with the trans-Golgi network and LC3-positive vesicles (shown in blue). Upon autophagy induction, Atg9 is mobilized away from the TGN to LC3-positive vesicles, which correlates with increased autophagosome synthesis. Our data show that overexpression of alpha-synuclein disrupts the normal localization and mobilization of Atg9 to LC3-positive vesicles, which correlates with decreased autophagosome synthesis and dysfunctional autophagy. This phenomenon may be a major contributor to PD pathogenesis, as inhibition of autophagy can increase aggregation, sensitivity to pro-apoptotic insults and mitochondrial dysfunction, all of which are associated with PD pathogenesis.

Similar articles

Cited by

References

    1. J Cell Biol. 2010 Sep 20;190(6):1023-37 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources