Apoptosis in the neuroprotective effect of a7 nicotinic receptor in neurodegenerative models

The & alpha;7 subtype of nicotinic receptors (& alpha;7 nAChRs) is one of the most abundant nicotinic receptor subtypes in the central nervous system (CNS) and both neurons and nonneuronal cells express & alpha;7 nAChRs. When activated, & alpha;7 nAChRs become permeable to cations and promote cellular responses such as anti-apoptotic signaling by modulating the caspases and proteins of the Bcl-2 family. Neuroprotection is an important function of these receptors, promoting neuronal survival under pathological conditions, including situations of stress and neuronal degeneration. Studies have demonstrated the relationship between the activation of these receptors and the reduction of neuronal or glial cell injury, by controlling apoptotic processes in different models, including neurodegenerative diseases such as Alzheimer's disease. Therefore, one of the most important signaling pathways activated by & alpha;7 nAChRs is the PI3K/Akt signaling cascade, which promotes the stimulation of anti-apoptotic molecules of the Bcl-2 family, Bcl-2 and Bcl-xl, and reduces the expression of caspases and proapoptotic molecules, resulting in cell survival. In Alzheimer's models, the literature shows that & alpha;7 nAChR activation attenuates A & beta;-induced neurotoxicity through modulation of different intrinsic apoptotic pathways via PI3K/Akt and mitogen-activated protein kinase (MAPK). In this review, we provide an up-to-date summary of the current evidence on the relationship between the activation of & alpha;7 nAChRs, a subtype of nicotinic acetylcholine receptor, and its role in neuroprotection by modulating apoptotic pathways.