α-synuclein interacts with SOD1 and promotes its oligomerization.

Authors :: Helferich AM
Ruf WP
Grozdanov V
Freischmidt A
Feiler MS
Zondler L
Ludolph AC
McLean PJ
Weishaupt JH
Danzer KM
Source :: Molecular neurodegeneration [Mol Neurodegener] 2015 Dec 08; Vol. 10, pp. 66. Date of Electronic Publication: 2015 Dec 08.
Publication Year :: 2015
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.<br />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.<br />Conclusion: This study provides evidence for a novel interaction of α-synuclein and SOD1 that might be relevant for neurodegenerative diseases.