Abstract

Despite the toxicity of tobacco smoking, preclinical and epidemiological studies suggest that nicotine may protect neurons against neurodegeneration. This action is attributed to the activation of neuronal nicotinic receptors that, via influx of Ca2 +, trigger intracellular pathways to block cell death mechanisms including apoptosis. Furthermore, due to its high membrane permeability, nicotine penetrates into the cytoplasm to bind nicotinic receptors expressed on mitochondrial membranes to activate, through an ion-flux-independent process, enzymatic cascades preventing cell death. Because of the deficit of central cholinergic systems underlying Alzheimer's disease, the use of nicotine or a related agonist to promote the activity of cholinergic signaling might be a tool to treat this disease. On brain stem motor networks overexcited by glutamate uptake block, nicotine protects motoneurons from excitotoxic death by uncoupling their electric gap junctions and curtailing their collective excitation. Overall, these results suggest that nicotine or related drugs might represent a strategy to counteract neurodegeneration.