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.

CONCLUSION:

This study provides evidence for a novel interaction of α-synuclein and SOD1 that might be relevant for neurodegenerative diseases.

• Authors: 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
• Journal: Molecular neurodegeneration (Mol Neurodegener) Vol. 10 Pg. 66 (Dec 08 2015) ISSN: 1750-1326 [Electronic] England
• PMID: 26643113 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• SNCA protein, human
• SOD1 protein, human
• Snca protein, mouse
• alpha-Synuclein
• Sod1 protein, mouse
• Superoxide Dismutase
• Superoxide Dismutase-1

Topics

• Amyotrophic Lateral Sclerosis (metabolism)
• Animals
• Brain (metabolism)
• Humans
• Mice, Transgenic
• Mutation (genetics)
• Parkinson Disease (metabolism)
• Protein Multimerization
• Superoxide Dismutase (metabolism)
• Superoxide Dismutase-1
• alpha-Synuclein (metabolism)