Will Smoking Stop Alzheimer’s Disease?
Will Smoking Stop Alzheimer’s Disease?
Source: Salomon AR, et al. Biochemistry 1996;35:13568-13578.
Nicotine is well known to most of us as a major component of cigarette smoke and is generally vilified as the pharmacological basis of smokers’ addiction. In research partially funded by a purveyor of tobacco products (the Philip Morris company), nicotine has been cast in a more positive light as a potent inhibitor of the aggregation of synthetic amyloid peptides, preventing the formation in a test-tube of the b-pleated sheets of amyloid that are characteristic of Alzheimer’s disease pathology in the brain.
Salomon and colleagues used a precipitation assay, a common approach to studying amyloid aggregation, and applied circular dichroism (CD) measurements and nuclear magnetic resonance (NMR) techniques to further characterize nicotine-amyloid b-peptide interactions. They used the synthetic b-(1-42) peptides in their aggregation studies because several lines of evidence have suggested that this form is the most "amyloidogenic." The addition of nicotine (at concentrations roughly 100 times greater than the peak level in the blood of an average smoker) to solutions containing b-(1-42) peptide (at concentrations roughly 1000-fold greater than are found in Alzheimer cerebrospinal fluid) led to a reduction in the rate of amyloid b-sheet formation sufficient to inhibit the precipitation of amyloid peptide completely. Various nicotine analogues were less efficacious in inhibiting precipitation and, in some cases, promoted the reaction. The NMR studies suggested that nicotine binds to a histidine residue within the a-helical structure of the b-peptide. It may, therefore, exert an inhibitory effect on amyloid precipitation by slowing the conversion of the a-helical structure to a b-sheet formation. —fp
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