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KMID : 0620920090410090611
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Experimental & Molecular Medicine
2009 Volume.41 No. 9 p.611 ~ p.617
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Intracellular amyloid beta interacts with SOD1 and impairs the enzymatic activity of SOD1: implications for the pathogenesis of amyotrophic lateral sclerosis
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Yoon Eun-Jin
Jang Ja-Young
Kang Seong-Man
Kim Goo-Young
Rhim Hyang-Shuk
Park Hyo-Jin
Cho Hyung-Min
Choi Jung-Ha
Park Hye-Yoon
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Abstract
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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 (Aβ) is associated with the pathogenesis of AD. In this report we demonstrate that intracellular Aβ directly interacts with SOD1, and that this interaction decreases the enzymatic activity of the enzyme. We observed Aβ-SOD1 aggregates in the perinuclear region of H4 cells, and mapped the SOD1 binding region to Aβ amino acids 26-42. Interestingly, intracellular Aβ 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 Aβ in the development of ALS by interacting with the SOD1 G93A mutant.
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KEYWORD
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Alzheimer disease, amyloid β-protein, amyotrophic lateral sclerosis, enzymology, protein interaction domains and motifs, superoxide dismutase 1
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