Proteasome inhibition induces α-synuclein SUMOylation and aggregate formation

Yong Man Kim, Won Hee Jang, Martha M. Quezado, Yohan Oh, Kwang Chul Chung, Eunsung Junn, M. Maral Mouradian

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61 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)157-161
Number of pages5
JournalJournal of the Neurological Sciences
Volume307
Issue number1-2
DOIs
Publication statusPublished - 2011 Aug 15

Bibliographical note

Funding Information:
This study was supported in part by the US NIH intramural program ( Z01NS002826 ) to M. M. M. who is currently the William Dow Lovett Professor of Neurology.

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

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