Nicotine and amyloid formation

Hong Zeng, Yongbo Zhang, Li Jun Peng, Haiyan Shao, Nanda K. Menon, Jing Yang, Arthur R. Salomon, Robert P. Freidland, Michael G. Zagorski*

*Corresponding author for this work

Research output: Contribution to journalReview article

69 Scopus citations

Abstract

The major protein constituents of amyloid deposits in Alzheimer's disease (AD) are the 40-residue β-amyloid (Aβ) (1-40) peptide and the 42-residue Aβ(1-42) peptide. The Aβ(1-42) is more pathogenic and produced in greater quantities in familial forms of AD. A major goal of research is to uncover a suitable inhibitor that either slows down or inhibits Aβ formation (β-amyloidosis). During β-amyloidosis, structural changes associated with the conversion of monomeric Aβ peptide building blocks into the aggregated fibrillar β-sheet structures occur (α-helix→β-sheet or random, extended chain→β-sheet). In previous work, we and others established that nicotine, a major component of cigarette smoke, inhibits β-amyloidosis of the Aβ(1-42), which may result from nicotine binding to the α-helical structure. These conclusions were based on solution nuclear magnetic resonance (NMR) spectroscopic studies with the nonnative 28-residue Aβ(1-28). This information suggests that, when administered therapeutically to AD patients, nicotine may not only affect cholinergic activation, but could also conceivably alter amyloid deposition. In this report, NMR studies were augmented with the naturally occurring Aβ(1-42), under conditions where the peptide folds into a predominantly α-helical or random, extended chain structure. The major result is that nicotine shows only modest binding to these conformations, indicating that the nicotine inhibition to β-amyloidosis probably results from binding to a small, soluble β-sheet aggregate that is NMR invisible.

Original languageEnglish (US)
Pages (from-to)248-257
Number of pages10
JournalBiological psychiatry
Volume49
Issue number3
DOIs
StatePublished - Feb 1 2001

Keywords

  • Alzheimer's disease
  • Amyloid
  • Aβ peptide
  • NMR
  • Nicotine

ASJC Scopus subject areas

  • Biological Psychiatry

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    Zeng, H., Zhang, Y., Peng, L. J., Shao, H., Menon, N. K., Yang, J., Salomon, A. R., Freidland, R. P., & Zagorski, M. G. (2001). Nicotine and amyloid formation. Biological psychiatry, 49(3), 248-257. https://doi.org/10.1016/S0006-3223(00)01111-2