Format

Send to

Choose Destination

See 1 citation found by title matching your search:

Mol Neurodegener. 2010 Nov 4;5:47. doi: 10.1186/1750-1326-5-47.

Parkinson-related parkin reduces α-Synuclein phosphorylation in a gene transfer model.

Author information

1
Department of Neuroscience, Georgetown University Medical Center, Washington D,C, U,S,A, 20007. cem46@georgetown.edu.

Abstract

BACKGROUND:

α-Synuclein aggregates in Lewy bodies and plays a central role in the pathogenesis of a group of neurodegenerative disorders, known as "Synucleinopathies", including Parkinson's disease. Parkin mutations result in loss of parkin E3-ubiquitin ligase activity and cause autosomal recessive early onset parkinsonism.

RESULTS:

We tested how these two genes interact by examining the effects of parkin on post-translational modification of α-Synuclein in gene transfer animal models, using a lentiviral gene delivery system into the striatum of 2-month old male Sprague Dawley rats.Viral expression of wild type α-Synuclein caused accumulation of α-Synuclein and was associated with increased cell death and inflammation. α-Synuclein increased PLK2 levels and GSK-3β activity and increased the levels of phosphorylated α-Synuclein and Tau. Parkin co-expression reduced the levels of phosphorylated α-Synuclein and attenuated cell death and inflammation. Parkin reduced PLK2 levels and increased PP2A activation.

CONCLUSIONS:

These data suggest that parkin reduces α-Synuclein levels and alters the balance between phosphatase and kinase activities that affect the levels of phosphorylated α-Synuclein. These results indicate novel mechanisms for parkin protection against α-Synuclein-induced toxicity in PD.

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center