Verification of the C-terminal intramolecular β-sheet in Aβ42 aggregates using solid-state NMR: Implications for potent neurotoxicity through the formation of radicals

Yuichi Masuda, Satoko Uemura, Azusa Nakanishi, Ryutaro Ohashi, K. Takegoshi, Takahiko Shimizu, Takuji Shirasawa, Kazuhiro Irie

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

Structural analysis of 42-residue amyloid β (Aβ42) aggregates using rotational resonance in solid-state NMR verified that Cβ and/or Cγ of Met-35 and the carboxyl carbon of Ala-42 are proximal enough to form an intramolecular antiparallel β-sheet in the C-terminus. The S-oxidized radical cation at Met-35, an ultimate radical species responsible for neurotoxicity, could be stabilized by the carboxylate anion at the C-terminus, resulting in aggregation to cause long-term oxidative stress.

Original languageEnglish
Pages (from-to)3206-3210
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume18
Issue number11
DOIs
Publication statusPublished - 2008 Jun 1

Keywords

  • Alzheimer's disease
  • Amyloid
  • Aβ42
  • Rotational resonance
  • Solid-state NMR
  • β-Sheet

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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