α-synuclein interacts with SOD1 and promotes its oligomerization

Background: Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) are both neurodegenerative diseases leading to impaired execution of movement. alpha-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 a-synuclein and SOD1 form oligomers and fibrils. In this study we investigated the possible molecular interaction of a-synuclein and SOD1 and its functional and pathological relevance. Results: Using a protein-fragment complementation approach and co-IP, we found that alpha-synuclein and SOD1 physically interact in living cells, human erythrocytes and mouse brain tissue. Additionally, our data show that disease related mutations in alpha-synuclein (A30P, A53T) and SOD1 (G85R, G93A) modify the binding of alpha-synuclein to SOD1. Notably, alpha-synuclein accelerates SOD1 oligomerization independent of SOD1 activity. Conclusion: This study provides evidence for a novel interaction of alpha-synuclein and SOD1 that might be relevant for neurodegenerative diseases.