# Analyzing Nicotine Action Against Amyloid Toxicity by NMR‐Pharmacometabolomics: An Exploratory Study

## TL;DR

This study explores how nicotine may protect against Alzheimer's disease by restoring metabolic imbalances caused by amyloid plaques.

## Contribution

The study provides new insights into nicotine's neuroprotective mechanism through NMR-based metabolomics in a cellular model of Alzheimer's.

## Key findings

- Nicotine reverses Aβ(1–42)-induced metabolic impairments in amino acid and energy metabolism.
- Nicotine influences neurotransmission and phospholipid metabolism in SH-SY5Y cells exposed to Aβ(1–42).

## Abstract

Alzheimer's disease (ad) is the primary neurodegenerative disease spread worldwide. One of the main histopathological hallmarks of ad is the deposition of amyloid plaques 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 gain new insights into the molecular mechanism underlying nicotine's neuroprotective action in ad, we performed NMR metabolomics on SH‐SY5Y neuroblastoma cells treated with Aβ(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 Aβ(1–42)‐induced metabolic impairments, including those related to amino acid metabolism, especially neurotransmission, as well as alterations in energy and membrane phospholipid metabolism.

Combined metabolomic analysis of the intracellular and extracellular portions of SH‐SY5Y cells revealed that, in the presence of Aβ 1–42, nicotine primarily influences pathways related to neurotransmission, energy metabolism, as well as the biosynthesis and degradation of membrane phospholipids.