α-突触核蛋白与超氧化物歧化酶1相互作用并促进其寡聚化。

α-synuclein interacts with SOD1 and promotes its oligomerization.

作者信息

Helferich Anika M, Ruf Wolfgang P, Grozdanov Veselin, Freischmidt Axel, Feiler Marisa S, Zondler Lisa, Ludolph Albert C, McLean Pamela J, Weishaupt Jochen H, Danzer Karin M

机构信息

Department of Neurology, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany.

Mayo Clinic, Jacksonville, Florida, USA.

出版信息

Mol Neurodegener. 2015 Dec 8;10:66. doi: 10.1186/s13024-015-0062-3.

BACKGROUND

Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) are both neurodegenerative diseases leading to impaired execution of movement. α-Synuclein plays a central role in the pathogenesis of PD whereas Cu, Zn superoxide dismutase (SOD1) is a key player in a subset of familial ALS cases. Under pathological conditions both α-synuclein and SOD1 form oligomers and fibrils. In this study we investigated the possible molecular interaction of α-synuclein and SOD1 and its functional and pathological relevance.

RESULTS

Using a protein-fragment complementation approach and co-IP, we found that α-synuclein and SOD1 physically interact in living cells, human erythrocytes and mouse brain tissue. Additionally, our data show that disease related mutations in α-synuclein (A30P, A53T) and SOD1 (G85R, G93A) modify the binding of α-synuclein to SOD1. Notably, α-synuclein accelerates SOD1 oligomerization independent of SOD1 activity.

CONCLUSION

This study provides evidence for a novel interaction of α-synuclein and SOD1 that might be relevant for neurodegenerative diseases.

背景

帕金森病（PD）和肌萎缩侧索硬化症（ALS）均为导致运动执行受损的神经退行性疾病。α-突触核蛋白在帕金森病的发病机制中起核心作用，而铜锌超氧化物歧化酶（SOD1）在一部分家族性肌萎缩侧索硬化症病例中是关键因素。在病理条件下，α-突触核蛋白和SOD1均会形成寡聚体和原纤维。在本研究中，我们调查了α-突触核蛋白与SOD1之间可能的分子相互作用及其功能和病理相关性。

结果

使用蛋白质片段互补方法和免疫共沉淀，我们发现α-突触核蛋白与SOD1在活细胞、人红细胞和小鼠脑组织中存在物理相互作用。此外，我们的数据表明，α-突触核蛋白（A30P、A53T）和SOD1（G85R、G93A）中的疾病相关突变会改变α-突触核蛋白与SOD1的结合。值得注意的是，α-突触核蛋白可加速SOD1寡聚化，且与SOD1活性无关。