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Molecular Neurodegeneration
Published in: Molecular Neurodegeneration 1/2010

Open Access 01-12-2010 | Research article

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

Authors: Preeti J Khandelwal, Sonya B Dumanis, Li Rebekah Feng, Kathleen Maguire-Zeiss, GW Rebeck, Hilal A Lashuel, Charbel EH Moussa

Published in: Molecular Neurodegeneration | Issue 1/2010

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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.
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Metadata
Title
Parkinson-related parkin reduces α-Synuclein phosphorylation in a gene transfer model
Authors
Preeti J Khandelwal
Sonya B Dumanis
Li Rebekah Feng
Kathleen Maguire-Zeiss
GW Rebeck
Hilal A Lashuel
Charbel EH Moussa
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2010
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/1750-1326-5-47

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