Apoptosis in the neuroprotective effect of α7 nicotinic receptor in neurodegenerative models

Abstract

The α7 subtype of nicotinic receptors (α7 nAChRs) is one of the most abundant nicotinic receptor subtypes in the central nervous system (CNS) and both neurons and nonneuronal cells express α7 nAChRs. When activated, α7 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 α7 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 α7 nAChR activation attenuates Aβ‐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 α7 nAChRs, a subtype of nicotinic acetylcholine receptor, and its role in neuroprotection by modulating apoptotic pathways.

Nicotinic Acetylcholine Receptors in Glial Cells as Molecular Target for Parkinson’s Disease

“…When activated, α7nAChRs allow the flow of cations, promoting cellular responses, including the modulation of the PI3K/Akt signaling cascade. This results in the anti-apoptotic stimulation of molecules of the Bcl-2 family, Bcl-2 and Bcl-xl, and the reduction of proapoptotic molecules, hence promoting cell survival [ 144 ]. α7nAChR is also a key protein in the cholinergic anti-inflammatory pathway (discussed in detail below) that links the nervous and the immune systems [ 145 ].…”

Nicotinic Acetylcholine Receptors in Glial Cells as Molecular Target for Parkinson’s Disease

“…When activated, α7nAChRs allow the flow of cations, promoting cellular responses including modulation of PI3K/Akt signaling cascade. This results in anti-apoptotic stimulation of molecules of the Bcl-2 family, Bcl-2 and Bcl-xl, and reduction of proapoptotic molecules, and hence promoting cell survival [144]. α7nAChR is also a key protein in the cholinergic anti-inflammatory pathway (discussed in detail below) that links the nervous and the immune systems [145].…”