Physiologic Functions and Therapeutic Applications of α7 Nicotinic Acetylcholine Receptor in Brain Disorders

Abstract

Accumulating data suggest that α7 nicotinic acetylcholine receptors (α7nAChRs) are an important therapeutic target for the treatment of Alzheimer’s disease (AD) and schizophrenia. The homopentameric ligand-gated ion channel α7nAChR consists of five identical α7 subunits that are encoded by the CHRNA7 (cholinergic receptor nicotinic alpha7 subunit) gene. Moreover, α7nAChRs are densely distributed throughout the hippocampus, cortex, and thalamus brain regions, but sparsely in the striatum, forebrain, and medulla. Compared with other nAChRs, α7nAChR binds with low affinity to the naturally occurring neurotransmitter acetylcholine and the non-specific exogenous agonist nicotine, and with high affinity to the specific antagonists α-bungarotoxin and methyllycaconitine. Reports indicate that α7nAChR plays important roles in neurotransmitter release, cognitive functioning, and the cholinergic anti-inflammatory response. Genetic variations that alter CHRNA7 mRNA and protein expression or cause α7nAChR dysfunction are associated with many brain disorders. Our previous studies revealed that α7nAChR exerts neuroprotection in AD by acting as a cargo receptor for binding the autophagosomal marker protein LC3 and engulfing extracellular neurotoxic Aβ1-42 during autophagic degradation of the α7nAChR-Aβ1-42 complex. However, the role of α7nAChRs in other diseases remains unknown. Here, we review and summarize the essential characteristics and current findings concerning α7nAChRs in four common brain diseases (AD, Parkinson’s disease, schizophrenia, and depression), which may elucidate the role of α7nAChRs and inform innovative research and novel treatments that target α7nAChRs in brain disease.

Evaluation of the effect of intraoperative tropisetron on postoperative rebound pain after brachial plexus block: a randomized controlled trial

“…Activation of a7nAch receptors has been demonstrated to ameliorate ischemic–reperfusion injury and provide neuroprotection. 32 In addition, we previously reported that tropisetron reduces inflammation and myocardial ischemic–reperfusion injury after heart valve replacement surgery. 11 Moreover, antagonism of 5HT-3 receptors has been shown to have anxiolytic effects on animal models through modulation of the serotonergic system.…”

New Multitarget Molecules Derived from Caffeine as Potentiators of the Cholinergic System

“…28 Great efforts are made to find new treatments for these diseases, and although the potentiation of the cholinergic system will not solve these pathological conditions, until now it is the main pharmacological strategy. 29 Through previous research, we identified caffeine as a new leader that can inhibit AChE and activate both muscle and α7 nAChR. 30 Caffeine behaves as a partial agonist at low micromolar concentrations and as an ion channel blocker at high micromolar concentrations.…”

“…As stated above, although there are different nAChR having distinct pharmacological profiles, muscle and α7 nAChR, both involved in myasthenic syndromes and in AD, are inhibited by α-bungarotoxin (α-BTX) . Great efforts are made to find new treatments for these diseases, and although the potentiation of the cholinergic system will not solve these pathological conditions, until now it is the main pharmacological strategy …”

Single-cell quantitative expression of nicotinic acetylcholine receptor mRNA in rat hippocampal interneurons

“…Understanding the scope of expression of nicotinic acetylcholine receptors (nAChRs) within hippocampal interneurons would lend great insight for cognitive therapies used in Alzheimer’s Disease [ 1 , 2 ], Attention-Deficit Hyperactivity Disorder [ 3 ], Autism Spectrum Disorder [ 4 ], and Post-Traumatic Stress Disorder [ 5 ]. The GABAergic interneurons are controlled by nAChRs found on their dendrites, soma, and on the axon terminals [ 6 ].…”