Proteasome inhibition induces α-synuclein SUMOylation and aggregate formation.
Proteasome inhibition induces α-synuclein SUMOylation and aggregate formation.
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DOI：
10.1016/j.jns.2011.04.015
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发表时间：
2011-08-15
影响因子：
4.4
通讯作者：
Mouradian, M. Maral
中科院分区：
文献类型：
--
作者：
Kim, Yong Man;Jang, Won Hee;Quezado, Martha M.;Oh, Yohan;Chung, Kwang Chul;Junn, Eunsung;Mouradian, M. Maral
关键词：
帕金森氏病(PD)和路易体痴呆(DLB)的病理特征是神经细胞内的包涵体，称为路易小体(Lbs)和路易氏突起。这些包涵体的一个主要成分是蛋白质α-突触核蛋白，它在自然情况下是不折叠的，但在病理条件下会形成寡聚体和不溶的纤维聚集体。虽然已知α-突触核蛋白经历了几次翻译后修饰，但SUMO化对α-突触核蛋白聚集的贡献以及α-突触核苷酸病的发病机制尚未阐明。在这里，我们提供的证据表明，由于蛋白酶体活性受损而形成的聚集体和包涵体含有SUMO化的α-突触核蛋白。此外，在PD和DLB患者的大脑中，SUMO1存在于与α-突触核蛋白共存的LBS的光环中。有趣的是，SUMO化并不影响α-突触核蛋白的泛素化。这些发现表明，蛋白酶体功能障碍导致SUMO化α-突触核蛋白的积聚，随后其聚集，表明这种翻译后修饰在α-突触核病症的包涵体形成机制中所起的作用。
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.
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影响因子：
56.9
作者：
Steffan, JS;Agrawal, N;Marsh, JL
通讯作者：
Marsh, JL
影响因子：
11.4
作者：
Johnson, ES;Schwienhorst, I;Blobel, G
通讯作者：
Blobel, G
DOI：
10.1016/s0006-291x(02)00211-5
发表时间：
2002-04-26
影响因子：
3.1
作者：
Ueda, H;Goto, J;Okazawa, H
通讯作者：
Okazawa, H
影响因子：
21.3
作者：
Fujiwara, H;Hasegawa, M;Iwatsubo, T
通讯作者：
Iwatsubo, T
影响因子：
9.8
作者：
Sandal M;Valle F;Tessari I;Mammi S;Bergantino E;Musiani F;Brucale M;Bubacco L;Samorì B
通讯作者：
Samorì B