Nicotine metabolite could hold back Alzheimer's

A chemical naturally present in tobacco appears to prevent one of
the markers of Alzheimer's disease, reported researchers in the US
recently.

A chemical naturally present in tobacco appears to prevent one of the markers of Alzheimer's disease, suggest researchers in the US.

They warn however that no link between smoking and prevention of the disease has been found.

The scientists from The Scripps Research Institute (TSRI) in California discovered that nornicotine, a nicotine metabolite, modifies proteins that form the fibril plaques abundant in the brains of Alzheimer's patients.

Combined with glucose, nornicotine attaches itself to amino acids on the surface of amyloid beta protein and prevents these proteins from misfolding and forming fibrils.

"This modification leads to decreased aggregation of the peptide,"​ said TSRI graduate student Tobin Dickerson. "In essence, this process physically blocks [the formation of the fibrils]."

However while the aggregation of amyloid beta protein is an accepted marker for Alzheimer's, it is not known whether these fibrils may be causing the disease or merely a marker. Nevertheless, Professor Kim Janda, an investigator in The Skaggs Institute for Chemical Biology at TSRI, said: "Nornicotine seems to prevent their [amyloid beta proteins] aggregation and, thus, could potentially impact the onset of Alzheimer's disease."

However he added that although nornicotine appears to have a positive effect, it is not likely that it would make a good therapeutic. The chemical is highly toxic and addictive.

But the research could lead to the development of small molecules similar to nornicotine that are not toxic but could behave in a similar fashion, preventing the aggregation of amyloid beta protein and perhaps treat Alzheimer's disease.

This work, published in the Proceedings of the National Academy of Sciences online edition on 16 June, also highlights the need for further study of the consequences of exposing the human body to nicotine metabolites, like nornicotine.

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