Proteasome inhibition induces α-synuclein SUMOylation and aggregate formation

JOURNAL OF THE NEUROLOGICAL SCIENCES

卷:307

Article

Kim, Yong Man²  Jang, Won Hee¹  Quezado, Martha M.³  Oh, Yohan⁴  Chung, Kwang Chul⁴  Junn, Eunsung¹  Mouradian, M. Maral¹ 

[1] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, Ctr Neurodegenerat & Neuroimmunol Dis, Piscataway, NJ 08854 USA

[2] FCB Pharmicell, Songnam 462806, Gyeonggi Do, South Korea

[3] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA

[4] Yonsei Univ, Coll Life Sci & Biotechnol, Dept Biol, Seoul 120749, South Korea

关键词: Parkinson's disease;    Dementia with Lewy Bodies;    alpha-Synuclein;    SUMOylation;    Protein aggregation;    Proteasome;   

DOI  :  10.1016/j.jns.2011.04.015

来源: Elsevier

【 摘 要 】

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 a-synuclein, which is natively unfolded but forms oligomers and insoluble fibrillar aggregates under pathological conditions. Although alpha-synuclein is known to undergo several posttranslational modifications, the contribution of SUMOylation to alpha-synuclein aggregation and the pathogenesis of alpha-synucleinopathies have not been elucidated. Here, we provide evidence that aggregates and inclusions formed as a result of impaired proteasome activity contain SUMOylated alpha-synuclein. Additionally, SUMO1 is present in the halo of LBs colocalizing with alpha-synuclein in the brains of PD and DLB patients. Interestingly. SUMOylation does not affect the ubiquitination of alpha-synuclein. These findings suggest that proteasomal dysfunction results in the accumulation of SUMOylated alpha-synuclein and subsequently its aggregation, pointing to the contribution of this posttranslational modification to the pathogenesis of inclusion formation in alpha-synucleinopathies. (C) 2011 Elsevier B.V. All rights reserved.

【 授权许可】

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