期刊
EXPERIMENTAL AND MOLECULAR MEDICINE
卷 41, 期 9, 页码 611-617出版社
NATURE PUBLISHING GROUP
DOI: 10.3858/emm.2009.41.9.067
关键词
Alzheimer disease; amyloid beta-protein; amyotrophic lateral sclerosis; enzymology; protein interaction domains and motifs; superoxide dismutase 1
资金
- Korean Government [R01-2007-000-20032-0]
- Korea Ministry of Health and Welfare [A080588-6]
- National Research Foundation of Korea [R01-2007-000-20032-0] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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 (A beta) is associated with the pathogenesis of AD. In this report we demonstrate that intracellular A beta directly interacts with SOD1, and that this interaction decreases the enzymatic activity of the enzyme. We observed A beta-SOD1 aggregates in the perinuclear region of H4 cells, and mapped the SOD1 binding region to A beta amino acids 26-42. Interestingly, intracellular A beta 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 A beta in the development of ALS by interacting with the SOD1 G93A mutant.
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