Exp Mol Med.  2009 Sep;41(9):611-617. 10.3858/emm.2009.41.9.067.

Intracellular amyloid beta interacts with SOD1 and impairs the enzymatic activity of SOD1: implications for the pathogenesis of amyotrophic lateral sclerosis

• Yoon EJ
• Park HJ
• Kim GY
• Cho H
• Choi JH
• Park HY
• Jang JY
• Rhim H
• Kang S

• KMID: 756204
• DOI: http://doi.org/10.3858/emm.2009.41.9.067

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the degeneration of motor neurons. Mutations in Cu/Zn superoxide dismutase (SOD1), including G93A, were reportedly linked to familial ALS. SOD1 is a key antioxidant enzyme, and is also one of the major targets for oxidative damage in the brains of patients suffering from Alzheimer's disease (AD). Several lines of evidence suggest that intracellular amyloid beta (Abeta) is associated with the pathogenesis of AD. In this report we demonstrate that intracellular Abeta directly interacts with SOD1, and that this interaction decreases the enzymatic activity of the enzyme. We observed Abeta-SOD1 aggregates in the perinuclear region of H4 cells, and mapped the SOD1 binding region to Abeta amino acids 26-42. Interestingly, intracellular Abeta binds to the SOD1 G93A mutant with greater affinity than to wild-type SOD1. This resulted in considerably less mutant enzymatic activity. Our study implicates a potential role for Abeta in the development of ALS by interacting with the SOD1 G93A mutant.

Keyword

Alzheimer disease; amyloid beta-protein; amyotrophic lateral sclerosis; enzymology; protein interaction domains and motifs; superoxide dismutase 1

MeSH Terms

Amino Acid Sequence
Amyloid beta-Protein/chemistry/*metabolism
Amyotrophic Lateral Sclerosis/*enzymology
Apoptosis
Cell Line
Cell Line, Tumor
Humans
Molecular Sequence Data
Point Mutation
Protein Binding
Protein Interaction Domains and Motifs
Superoxide Dismutase/genetics/*metabolism