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

Research output: Contribution to journalArticle

24 Citations (Scopus)

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 (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
Volume41
Issue number9
DOIs
Publication statusPublished - 2009 Sep 30

Fingerprint

Amyotrophic Lateral Sclerosis
Amyloid
Alzheimer Disease
Neurodegenerative diseases
Motor Neurons
Enzymes
Neurodegenerative Diseases
Neurons
Brain
Antioxidants
Amino Acids
Mutation
Superoxide Dismutase-1
Amyotrophic lateral sclerosis 1
Superoxide Dismutase

Keywords

  • 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

Cite this

Intracellular amyloid beta interacts with SOD1 and impairs the enzymatic activity of SOD1 : Implications for the pathogenesis of amyotrophic lateral sclerosis. / Eun, Jin Yoon; Park, Hyo Jin; Kim, Goo Young; Cho, Hyungmin; Choi, Jung Ha; Park, Hye Yoon; Jang, Ja Young; Rhim, Hyangshuk; Kang, Seong Man.

In: Experimental and Molecular Medicine, Vol. 41, No. 9, 30.09.2009, p. 611-617.

Research output: Contribution to journalArticle

Eun, Jin Yoon ; Park, Hyo Jin ; Kim, Goo Young ; Cho, Hyungmin ; Choi, Jung Ha ; Park, Hye Yoon ; Jang, Ja Young ; Rhim, Hyangshuk ; Kang, Seong Man. / Intracellular amyloid beta interacts with SOD1 and impairs the enzymatic activity of SOD1 : Implications for the pathogenesis of amyotrophic lateral sclerosis. In: Experimental and Molecular Medicine. 2009 ; Vol. 41, No. 9. pp. 611-617.
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