title: α-synuclein interacts with SOD1 and promotes its oligomerization.
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.
  
  
  CONCLUSIONS
  This study provides evidence for a novel interaction of α-synuclein and SOD1 that might be relevant for neurodegenerative diseases.
authors.affiliation: Department of Neurology, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
authors.forename: Anika M
authors.initials: AM
authors.lastname: Helferich
authors.affiliation: Department of Neurology, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
authors.forename: Wolfgang P
authors.initials: WP
authors.lastname: Ruf
authors.affiliation: Department of Neurology, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
authors.forename: Veselin
authors.initials: V
authors.lastname: Grozdanov
authors.affiliation: Department of Neurology, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Freischmidt
authors.affiliation: Department of Neurology, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
authors.forename: Marisa S
authors.initials: MS
authors.lastname: Feiler
authors.affiliation: Department of Neurology, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Zondler
authors.affiliation: Department of Neurology, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
authors.forename: Albert C
authors.initials: AC
authors.lastname: Ludolph
authors.affiliation: Mayo Clinic, Jacksonville, Florida, USA.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: McLean
authors.affiliation: Department of Neurology, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
authors.forename: Jochen H
authors.initials: JH
authors.lastname: Weishaupt
authors.affiliation: Department of Neurology, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany. karin.danzer@uni-ulm.de.
authors.forename: Karin M
authors.initials: KM
authors.lastname: Danzer
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D006801:Humans; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D010300:Parkinson Disease / Q000378:metabolism; D055503:Protein Multimerization; D013482:Superoxide Dismutase / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: C497604:SNCA protein, human; C000606290:SOD1 protein, human; C497605:Snca protein, mouse; D051844:alpha-Synuclein; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1