Α-synuclein interacts with SOD1 and promotes its oligomerization. Issue 1 (December 2015)

• Record Type: Journal Article
• Authors: Helferich, Anika; Ruf, Wolfgang; Grozdanov, Veselin; Freischmidt, Axel; Feiler, Marisa; Zondler, Lisa; Ludolph, Albert; McLean, Pamela; Weishaupt, Jochen; Danzer, Karin
• Is Part Of: Molecular neurodegeneration. Volume 10:Issue 1(2015)
• Page Start: 1
• Page End: 16
• Publication Date: 2015-12
• Subjects: Alpha synuclein -- SNCA -- SOD1 -- ALS -- Parkinson's disease -- Cross-seeding -- Oligomers; Neurobiology -- Periodicals; Nervous system -- Diseases -- Periodicals; 616.8
• DOI: 10.1186/s13024-015-0062-3
• Languages: English
• ISSNs: 1750-1326

Abstract

Abstract 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.