Screening of drugs inhibiting in vitro oligomerization of Cu/Zn-superoxide dismutase with a mutation causing amyotrophic lateral sclerosis

Itsuki Anzai, Keisuke Toichi, Eiichi Tokuda, Atsushi Mukaiyama, Shuji Akiyama, Yoshiaki Furukawa

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Dominant mutations in Cu/Zn-superoxide dismutase (SOD1) gene have been shown to cause a familial form of amyotrophic lateral sclerosis (SOD1-ALS). A major pathological hallmark of this disease is abnormal accumulation of mutant SOD1 oligomers in the affected spinal motor neurons. While no effective therapeutics for SOD1-ALS is currently available, SOD1 oligomerization will be a good target for developing cures of this disease. Recently, we have reproduced the formation of SOD1 oligomers abnormally cross-linked via disulfide bonds in a test tube. Using our in vitro model of SOD1 oligomerization, therefore, we screened 640 FDA-approved drugs for inhibiting the oligomerization of SOD1 proteins, and three effective classes of chemical compounds were identified. Those hit compounds will provide valuable information on the chemical structures for developing a novel drug candidate suppressing the abnormal oligomerization of mutant SOD1 and possibly curing the disease.

Original languageEnglish
Article number40
JournalFrontiers in Molecular Biosciences
Volume3
Issue numberAUG
DOIs
Publication statusPublished - 2016 Aug 9

Keywords

  • Amyotrophic lateral sclerosis
  • Cu/Zn-superoxide dismutase
  • Drug screening
  • Protein aggregation
  • Protein misfolding

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)

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