Polo-like kinase 2 regulates selective autophagic α-synuclein clearance and suppresses its toxicity in vivo
Abstract
Converging lines of evidence suggest that increase in α-syn levels plays a central role in synucleinopathies pathogenesis. Therefore, lowering α-syn levels represents a viable therapeutic strategy for these disorders. Here, we describe a previously uncharacterized cellular mechanism controlling the selective autophagic degradation of α-syn. This effect is governed by PLK2 kinase activity, phosphorylation of α-syn, and PLK2/α-syn complex formation. In a rat model of Parkinson disease, PLK2 overexpression reduces α-syn levels and suppresses α-syn-induced toxicity and motor deficits. Collectively, our data support the neuroprotective role of PLK2 and suggest that modulating its activity is a viable therapeutic strategy for the treatment of Parkinson disease and related synucleinopathies.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- October 2013
- DOI:
- 10.1073/pnas.1309991110
- Bibcode:
- 2013PNAS..110E3945O