Intracellular amyloid beta interacts with SOD1 and impairs the enzymatic activity of SOD1: implications for the pathogenesis of amyotrophic lateral sclerosis.
10.3858/emm.2009.41.9.067
- Author:
Eun Jin YOON
1
;
Hyo Jin PARK
;
Goo Young KIM
;
Hyungmin CHO
;
Jung Ha CHOI
;
Hye Yoon PARK
;
Ja Young JANG
;
Hyangshuk RHIM
;
Seongman KANG
Author Information
1. School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea. skang@korea.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Alzheimer disease;
amyloid beta-protein;
amyotrophic lateral sclerosis;
enzymology;
protein interaction domains and motifs;
superoxide dismutase 1
- MeSH:
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
- From:Experimental & Molecular Medicine
2009;41(9):611-617
- CountryRepublic of Korea
- Language:English
-
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.
