α-synuclein interacts with SOD1 and promotes its oligomerization.

Autor: Helferich AM; Department of Neurology, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany., Ruf WP; Department of Neurology, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany., Grozdanov V; Department of Neurology, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany., Freischmidt A; Department of Neurology, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany., Feiler MS; Department of Neurology, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany., Zondler L; Department of Neurology, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany., Ludolph AC; Department of Neurology, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany., McLean PJ; Mayo Clinic, Jacksonville, Florida, USA., Weishaupt JH; Department of Neurology, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany., Danzer KM; Department of Neurology, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany. karin.danzer@uni-ulm.de.
Jazyk: angličtina
Zdroj: Molecular neurodegeneration [Mol Neurodegener] 2015 Dec 08; Vol. 10, pp. 66. Date of Electronic Publication: 2015 Dec 08.
DOI: 10.1186/s13024-015-0062-3
Abstrakt: 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.
Databáze: MEDLINE
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