NR AFBV
AU Han,H.Y.; Weinreb,P.H.; Lansbury,P.T.Jr.
TI The core Alzheimer's peptide NAC forms amyloid fibrils which seed and are seeded by beta-amyloid: is NAC a common trigger or target in neurodegenerative disease?
QU Chemistry and Biology 1995 Mar; 2(3): 163-9
PT journal article
AB 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 alpha-synuclein (or NACP), a neuronal protein of unknown function. We noted a striking sequence similarity between NAC, the carboxyl terminus of the beta-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 beta 1-40 amyloid formation. Amyloid fibrils comprising peptide models of the homologous beta 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 beta-amyloid protein, or seeding of amyloid fibrils of the beta-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 alpha-synuclein (NACP) function.
IN Das Alpha-Synuclein-Protein in den amyloiden Plaques der Alzheimer-Krankheit zeigt offenbar eine Homologie zum Prionprotein.
MH Amino Acid Sequence; Amyloid/chemical synthesis/*chemistry/metabolism; Amyloid beta-Protein/*chemistry; Chemistry, Physical; Crystallization; Human; Kinetics; Microscopy, Electron; Molecular Sequence Data; Nerve Degeneration/*metabolism; Solubility; Solutions; Spectroscopy, Fourier Transform Infrared; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Synapses/metabolism
AD Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139, USA
SP englisch
PO England