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

Research output: Contribution to journalArticle

47 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

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Synucleins
Sumoylation
Proteasome Endopeptidase Complex
Lewy Bodies
Lewy Body Disease
Post Translational Protein Processing
Parkinson Disease
Ubiquitination
Brain Diseases
Neurites
Inhibition (Psychology)

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

Kim, Yong Man ; Jang, Won Hee ; Quezado, Martha M. ; Oh, Yohan ; Chung, Kwang Chul ; Junn, Eunsung ; Mouradian, M. Maral. / Proteasome inhibition induces α-synuclein SUMOylation and aggregate formation. In: Journal of the Neurological Sciences. 2011 ; Vol. 307, No. 1-2. pp. 157-161.
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Proteasome inhibition induces α-synuclein SUMOylation and aggregate formation. / Kim, Yong Man; Jang, Won Hee; Quezado, Martha M.; Oh, Yohan; Chung, Kwang Chul; Junn, Eunsung; Mouradian, M. Maral.

In: Journal of the Neurological Sciences, Vol. 307, No. 1-2, 15.08.2011, p. 157-161.

Research output: Contribution to journalArticle

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