α-Synuclein interacts with SOD1 and promotes its oligomerization

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

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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.

Original languageEnglish (US)
Article number66
JournalMolecular neurodegeneration
Volume10
Issue number1
DOIs
StatePublished - Dec 8 2015

Keywords

  • ALS
  • Alpha synuclein
  • Cross-seeding
  • Oligomers
  • Parkinson's disease
  • SNCA
  • SOD1

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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