Current Landscape for Research and Development of α7-Nicotine Acetylcholine Receptor Targeting Positive Allosteric Modulators for Improvement of Cognitive Impairment

With the aggravation of global problem of aging, Alzheimer's disease has become one of the major threats of human health. At present, there are no effective drugs that can significantly improve cognitive function of patients with Alzheimer's disease, which presents an unmet medical need and an extreme challenge. Studies have shown that enhancing α7-nicotine acetylcholine receptor (nAChR) function can improve cognitive impairment and neuroimmunity. Distinct from agonists, α7 positive allosteric modulators (α7 PAMs) enhance the function of nAChR only in the presence of endogenous transmitter acetylcholine, and are also characterized by less desensitization and potential toxic and side effects. Therefore, targeting α7 by PAMs emerges as a new strategy for potential treatment of Alzheimer's disease. This review focuses on recent literature and our research progress on the discovery of α7 nAChR PAMs and their biological evaluation, which is expected to promote the research and development of novel α7 nAChR PAMs for improvement of cognitive impairment common to neuropsychiatric disorders.