Isomerization and/or racemization at Asp23 of Aβ42 do not increase its aggregative ability, neurotoxicity, and radical productivity in vitro

Kazuma Murakami, Mayumi Uno, Yuichi Masuda, Takahiko Shimizu, Takuji Shirasawa, Kazuhiro Irie

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Aggregation of the 42-mer amyloid β peptide (Aβ42) plays a pivotal role in the pathogenesis of Alzheimer's disease. Recent investigations suggested the isomerization and/or racemization of Asp at position 1, 7, or 23 to be associated with the pathological role of Aβ42. Our previous study indicated that the turn at positions 22 and 23 of Aβ42 is closely related to its neurotoxicity through the formation of radicals. To clarify the contribution of these modifications at Asp23 to the pathology, three isomerized and/or racemized Aβ42 mutants were prepared. l-isoAsp23- and d-Asp23-Aβ42 showed moderate aggregative ability similar to the wild type. However, d-Asp23-Aβ42 was less neurotoxic than the wild type, while l-isoAsp23-Aβ42 was as toxic as the wild type. In contrast, d-isoAsp23-Aβ42 showed weak aggregative ability without neurotoxicity. These results suggest the isomerization and/or racemization of Asp23 not to be related to the pathogenesis, but to be a consequence of chemical reactions during the long-term deposition of fibrils.

Original languageEnglish
Pages (from-to)745-751
Number of pages7
JournalBiochemical and biophysical research communications
Volume366
Issue number3
DOIs
Publication statusPublished - 2008 Feb 15

Keywords

  • Aggregation
  • Alzheimer's disease
  • Amyloid
  • ESR
  • Isomerization
  • MTT
  • Neurotoxicity
  • PC12
  • Racemization
  • Thioflavin-T

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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