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bioRxiv · 10.1101/2025.09.03.673931

Analyzing nicotine action against amyloid toxicity by NMR-pharmacometabolomics: an exploratory study.

Napolitano, E.·Marino, C.·Grimaldi, M.·Buonocore, M.·D'Ursi, A. M.
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Abstract

Alzheimers disease (AD) is the primary neurodegenerative disease spread worldwide. One of the main histopathological hallmarks of AD is amyloid plaque deposition in the brain. Despite some epidemiological studies demonstrating that cigarette smoke is a factor in predisposing people to AD, nicotine, the principal alkaloid of Nicotiana Tobacco, has been widely studied for its ability to improve cognitive performance, both in animal models and in human studies. Several hypotheses have been proposed to explain the mechanism of action underlying the beneficial effect of Nicotine in AD; however, this is still questioned. To have new insights into the molecular mechanism underlying the neuroprotective action of Nicotine in Alzheimers disease, we performed an NMR metabolomic analysis of SH-SY5Y neuroblastoma cells treated with A{beta} (1-42) in the presence of nicotine. Our data show that the neuroprotective action of nicotine resides in its ability to restore the systemic unbalanced metabolism associated with AD. In particular, nicotine reverses most A{beta} (1-42)-induced metabolic impairments, including those related to amino acid metabolism, especially those involved in neurotransmission, as well as alterations in energy metabolism and membrane phospholipid metabolism.

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Napolitano, E., Marino, C., Grimaldi, M., Buonocore, M., D'Ursi, A. M.. 2025-09-06. Analyzing nicotine action against amyloid toxicity by NMR-pharmacometabolomics: an exploratory study.. https://doi.org/10.1101/2025.09.03.673931

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