Mechanisms of Nicotine-Induced Neuroprotection: Inhibition of NADPH Oxidase and Subsequent Proton Channel Activation by Stimulating α7 Nicotinic Acetylcholine Receptor in Activated Microglia
Restricted accessReview articleFirst published online May, 2016
Mechanisms of Nicotine-Induced Neuroprotection: Inhibition of NADPH Oxidase and Subsequent Proton Channel Activation by Stimulating α7 Nicotinic Acetylcholine Receptor in Activated Microglia
Alpha 7 subunits of nicotinic acetylcholine receptors (nAChRs) are expressed in microglia and astrocyte and are involved in the suppression of neuroinflammation. Over the past decade, many reports show beneficial effects of nicotine. Here we review the function of nAChR in glial cells and how nicotine attenuates neuronal death induced by activated microglia. One is Ca2+-dependent action. Nicotine causes transienct increase in intracellular Ca2+ in phospholipase C (PLC)/inositol 1,4,5-trisphosphate (IP3)-dependent manner, and negatively modulates LPS-induced release of pro-inflammatory cytokines. The seconed is adenine dinucleotide phosphate (NADPH) oxidase (NOX)-dependent action. Nicotine may attenuate NOX and subsequently inhibiting acidosis, therefore inhibit activation of H+ channel in activated microglia. The inhibitory effect of nicotine on H+ current is due to the activation of α7 nAChR. On the other hand, nicotine does not affect increased expression of H+ channel, HVCN1, in activated microglia. Especially the phagocytic NOX (NOX2) is the best studied ROS-generating system and is mainly expressed in microglia in the CNS. Since a role of NOX2 in Alzheimer's and cerebrovascular disease and other neurological diseases relating to smoking is implicated, inhibiting NOX2 and consecutive acidosis and activation of H+ channel in microglia may have a therapeutic potential in neuroinflammatory diseases.
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