Ganglioside Nanocluster-Targeting Peptidyl Inhibitor Prevents Amyloid β Fibril Formation on the Neuronal Membrane

Teruhiko Matsubara, Mako Nakai, Masaya Nishihara, Erika Miyamoto, Toshinori Sato

研究成果: Article査読

抄録

Neurotoxicity caused by peptide and protein aggregates is associated with the onset of neurodegenerative diseases. Accumulation of the amyloid β protein (Aβ) induced by neuronal ganglioside-enriched nanodomains (nanoclusters) in the presynaptic neuronal membrane, resulting in toxic oligomeric and fibrous forms, is implicated in the onset of Alzheimer's disease (AD). In the current study, we found that the ganglioside cluster-binding peptide (GCBP), a pentadecapeptide VWRLLAPPFSNRLLP that binds to ganglioside-enriched nanoclusters, inhibits the formation of Aβ assemblies with an IC50 of 12 pM and also removes Aβ fibrils deposited on the lipid membrane. Thus, in addition to inhibiting Aβ assembly formation, GCBP effectively clears toxic Aβ assemblies as well, thereby suppressing neuronal cellular damage and death induced by such assemblies. These results indicate that ganglioside cluster-binding molecules may act as novel Aβ-targeting drugs with a unique mechanism of action that may be utilized to ameliorate AD.

本文言語English
ページ(範囲)1868-1876
ページ数9
ジャーナルACS Chemical Neuroscience
13
13
DOI
出版ステータスPublished - 2022 7月 6

ASJC Scopus subject areas

  • 生化学
  • 生理学
  • 認知神経科学
  • 細胞生物学

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