Nicotine and amyloid formation

Citation
H. Zeng et al., Nicotine and amyloid formation, BIOL PSYCHI, 49(3), 2001, pp. 248-257
Citations number
57
Categorie Soggetti
Neurosciences & Behavoir
Journal title
BIOLOGICAL PSYCHIATRY
ISSN journal
00063223 → ACNP
Volume
49
Issue
3
Year of publication
2001
Pages
248 - 257
Database
ISI
SICI code
0006-3223(20010201)49:3<248:NAAF>2.0.ZU;2-7
Abstract
The major protein constituents of amyloid deposits in Alzheimer's disease ( AD) are the 40-residue beta -amyloid (A beta) (1-40) peptide and the 42-res idue A beta (1-42) peptide. The A beta (1-42) is more pathogenic and produc ed 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 A bet a formation (beta -amyloidosis). During beta -amyloidosis, structural chang es associated with the conversion of monomeric A beta peptide building bloc ks into the aggregated fibrillar beta -sheet structures occur (alpha -helix -->beta -sheet or random, extended chain-->beta -sheet). In previous work, we and others established that nicotine, a major component of cigarette smo ke, inhibits beta -amyloidosis of the A beta (1-42), which may result from nicotine binding to the alpha -helical structure. These conclusions were ba sed on solution nuclear magnetic resonance (NMR) spectroscopic studies with the nonnative 28-residue A beta (1-28). This information suggests that, wh en administered therapeutically to AD patients, nicotine may not only affec t cholinergic activation, but could also conceivably alter amyloid depositi on. In this report, NMR studies were augmented with the naturally occurring A beta (1-42), under conditions where the peptide folds into a predominant ly alpha -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 beta -amyloidosis probably results from bin ding to a small, soluble beta -sheet aggregate that is NMR invisible. (C) 2 001 Society of Biological Psychiatry.