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

244 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 prepared by chemical synthesis and was found to form amyloid fibrils via a nucleation-dependent polymerization mechanism. NAC amyloid fibrils effectively seed β1-40 amyloid formation. 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
Publication statusPublished - 1995 Dec 1
Externally publishedYes

Fingerprint

Neurodegenerative diseases
Amyloid
Neurodegenerative Diseases
Seed
Seeds
Peptides
Amyloidogenic Proteins
Synucleins
Alzheimer Disease
Scrapie
Prions
Amyloid Plaques
Polymerization
Synapses
Nucleation
Amino Acids

Keywords

  • α-synuclein
  • β-amyloid
  • NAC
  • Prion
  • Seeding

ASJC Scopus subject areas

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

Cite this

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? / Han, Hogyu; Weinreb, Paul H.; Lansbury, Peter T.

In: Chemistry and Biology, Vol. 2, No. 3, 01.12.1995, p. 163-169.

Research output: Contribution to journalArticle

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