The α7 nAChR selective agonists as drug candidates for alzheimer’s disease

Abstract

The nicotinic acetylcholine receptors (nAChRs) are ion channels distribute in the central or peripheral nervous system. They are receptors of the neurotransmitter acetylcholine and activation of them by agonists mediates synaptic transmission in the neuron and muscle contraction in the neuromuscular junction. Current studies reveal relationship between the nAChRs and the learning and memory as well as cognation deficit in various neurological disorders such as Alzheimer’s disease, Parkinson’s disease, schizophrenia and drug addiction. There are various subtypes in the nAChR family and the α7 nAChR is one of the most abundant subtypes in the brain. The α7 nAChR is significantly reduced in the patients of Alzheimer’s disease and is believed to interact with the Aβ amyloid. Aβ amyloid is co-localized with α7 nAChR in the senile plaque and interaction between them induces neuron apoptosis and reduction of the α7 nAChR expression. Treatment with α7 agonist in vivo shows its neuron protective and procognation properties and significantly improves the learning and memory ability of the animal models. Therefore, the a7 nAChR agonists are excellent drug candidates for Alzheimer’s disease and we summarized here the current agonists that have selectivity of the α7 nAChR over the other nAChR, introduced recent molecular modeling works trying to explain the molecular mechanism of their selectivity and described the design of novel allosteric modulators in our lab.