| Literature DB >> 21641618 |
Yong Man Kim1, Won Hee Jang, Martha M Quezado, Yohan Oh, Kwang Chul Chung, Eunsung Junn, M Maral Mouradian.
Abstract
Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB) are characterized pathologically by intraneuronal inclusions called Lewy bodies (LBs) and Lewy neurites. A major component of these inclusions is the protein α-synuclein, which is natively unfolded but forms oligomers and insoluble fibrillar aggregates under pathological conditions. Although α-synuclein is known to undergo several posttranslational modifications, the contribution of SUMOylation to α-synuclein aggregation and the pathogenesis of α-synucleinopathies have not been elucidated. Here, we provide evidence that aggregates and inclusions formed as a result of impaired proteasome activity contain SUMOylated α-synuclein. Additionally, SUMO1 is present in the halo of LBs colocalizing with α-synuclein in the brains of PD and DLB patients. Interestingly, SUMOylation does not affect the ubiquitination of α-synuclein. These findings suggest that proteasomal dysfunction results in the accumulation of SUMOylated α-synuclein and subsequently its aggregation, pointing to the contribution of this posttranslational modification to the pathogenesis of inclusion formation in α-synucleinopathies.Entities:
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Year: 2011 PMID： 21641618 PMCID： PMC3129438 DOI： 10.1016/j.jns.2011.04.015
Source DB: PubMed Journal: J Neurol Sci ISSN： 0022-510X Impact factor: 3.181