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

Jin Yoon Eun, Hyo Jin Park, Goo Young Kim, Hyungmin Cho, Jung Ha Choi, Hye Yoon Park, Ja Young Jang, Hyangshuk Rhim, Seong Man Kang

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25 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)611-617
Number of pages7
JournalExperimental and Molecular Medicine
Issue number9
Publication statusPublished - 2009 Sep 30



  • Alzheimer disease
  • Amyloid β-protein
  • Amyotrophic lateral sclerosis
  • Enzymology
  • Protein interaction domains and motifs
  • Superoxide dismutase 1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Clinical Biochemistry

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