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Titolo:
NICOTINE INHIBITS AMYLOID FORMATION BY THE BETA-PEPTIDE
Autore:
SALOMON AR; MARCINOWSKI KJ; FRIEDLAND RP; ZAGORSKI MG;
Indirizzi:
CASE WESTERN RESERVE UNIV,SCH MED,DEPT CHEM CLEVELAND OH 44106 CASE WESTERN RESERVE UNIV,SCH MED,DEPT CHEM CLEVELAND OH 44106 CASE WESTERN RESERVE UNIV,SCH MED,DEPT NEUROL CLEVELAND OH 44106
Titolo Testata:
Biochemistry
fascicolo: 42, volume: 35, anno: 1996,
pagine: 13568 - 13578
SICI:
0006-2960(1996)35:42<13568:NIAFBT>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
SHORT-TERM-MEMORY; PROTEIN A-BETA; ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; SECONDARY STRUCTURE; FIBRIL FORMATION; CONFORMATIONAL TRANSITIONS; PRECURSOR PROTEIN; SENILE PLAQUES; PRION PROTEIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
96
Recensione:
Indirizzi per estratti:
Citazione:
A.R. Salomon et al., "NICOTINE INHIBITS AMYLOID FORMATION BY THE BETA-PEPTIDE", Biochemistry, 35(42), 1996, pp. 13568-13578

Abstract

The 42-residue beta-(1-42) peptide is the major protein component of amyloid plaque cores in Alzheimer's disease. In aqueous solution at physiological pH, the synthetic beta-(1-42) peptide readily aggregates and precipitates as oligomeric beta-sheet structures, a process that occurs during amyloid formation in Alzheimer's disease. Using circular dichroism (CD) and ultraviolet spectroscopic techniques, we show that nicotine, a major component in cigarette smoke, inhibits amyloid formation by the beta-(1-42) peptide. The related compound cotinine, the major metabolite of nicotine in humans, also slows down amyloid formation, but to a lesser extent than nicotine, In contrast, control substances pyridine and N-methylpyrrolidine accelerate the aggregation process. Nuclear magnetic resonance (NMR) studies demonstrate that nicotine binds to the 1-28 peptide region when folded in an alpha-helical conformation. On the basis of chemical shift data, the binding primarily involves the N-CH3 and 5'CH2 pyrrolidine moieties of nicotine and the histidine residues of the peptide. The binding is in fast exchange, as shown by single averaged NMR peaks and the lack of-nuclear Overhauser enhancement data between nicotine and the peptide in two-dimensional NOESY spectra. A mechanism is preposed, whereby nicotine retards amyloidosis by preventing an alpha-helix-->beta-sheet conformational transformation that is important in the pathogenesis of Alzheimer's disease.

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Documento generato il 24/11/20 alle ore 14:15:59