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

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15 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

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Keywords

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

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Clinical Neurology
  • Molecular Biology

Cite this

Helferich, A. M., Ruf, W. P., Grozdanov, V., Freischmidt, A., Feiler, M. S., Zondler, L., Ludolph, A. C., McLean, P. J., Weishaupt, J. H., & Danzer, K. M. (2015). α-Synuclein interacts with SOD1 and promotes its oligomerization. Molecular Neurodegeneration, 10(1), [66]. https://doi.org/10.1186/s13024-015-0062-3