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.
Funder
the Ministry of Science and Technology of Taiwan
China Medical University
Reference99 articles.
1. Carlson, A.B., and Kraus, G.P. (2022). Physiology, Cholinergic Receptors, StatPearls.
2. Novel insights into muscarinic acetylcholine receptor function using gene targeting technology;Wess;Trends Pharmacol. Sci.,2003
3. Molecular evolution of the nicotinic acetylcholine receptor: An example of multigene family in excitable cells;Changeux;J. Mol. Evol.,1995
4. Nicotinic receptors that bind alpha-bungarotoxin on neurons raise intracellular free Ca2+;Vijayaraghavan;Neuron,1992
5. Hogg, R.C., Raggenbass, M., and Bertrand, D. (2003). Reviews of Physiology, Biochemistry and Pharmacology, Springer.
Cited by
5 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献