The core Alzheimer's peptide NAC forms amyloid fibrils which seed and are seeded by β-amyloid: is NAC a common trigger or target in neurodegenerative disease?

Hogyu Han, Paul H. Weinreb, Peter T. Lansbury

Research output: Contribution to journalArticle

252 Citations (Scopus)

Abstract

Background: NAC is a 35-amino-acid peptide which has been isolated from the insoluble core of Alzheimer's disease (AD) amyloid plaque. It is a fragment of α-synuclein or (NACP), a neuronal protein of unknown function. We noted a striking sequence similarity between NAC, the carboxyl terminus of the β-amyloid protein, and a region of the scrapie prion protein (PrP) which has been implicated in amyloid formation. Results: NAC was preprared by chemical synthesis and was found to form amuloid fibrils via a nucleotion-dependent polymerization mechanism. NAC amyloid fibrils effectively seed β1-40 amyloid ormation. Amyloid fibrils comprising peptide models of the homologous β and PrP sequences were also found to seed amyloid formation by NAC. Conclusions: The in vitro model studies presented here suggest that seeding of NAC amyloid formation by the β-amyloid protein, or seeding of amyloid fibrils of the β-amyloid protein by NAC, may occur in vivo. Accumulation of ordered NAC aggregates in the synapse may be responsible for the neurodegeneration observed in AD and the prion disorders. Alternatively, neurodegeneration may be caused by the loss of α-synuclein (NACP) function.

Original languageEnglish
Pages (from-to)163-169
Number of pages7
JournalChemistry and Biology
Volume2
Issue number3
DOIs
Publication statusPublished - 1995 Mar

Keywords

  • NAC
  • prion
  • seeding
  • α-synuclein
  • β-amyloid

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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