title: Allosteric Modulation of Nicotinic Acetylcholine Receptors: The Concept and Therapeutic Trends.
abstract: Expressing functional nicotinic acetylcholine receptors (nAChRs) may be beneficial to central neurons and neuronal networks because activation of nAChRs enhances neuronal resistance to injury, improves attention, cognitive performance, and produces robust anti-inflammatory and analgesic effects in mammals. Although exogenous orthosteric nAChR ligands present valuable tools in treatment of age- and trauma-related neurological deficits, therapeutic approaches that could amplify the brain's innate ability to maintain cholinergic homeostasis and resist injury may serve as intriguing and promising alternatives and have not been fully explored. One of these novel approaches utilizes positive allosteric modulators (PAMs) of nAChRs. Because of the ubiquitous expression of nAChRs in neuronal, glial and immune tissues, highly selective PAMs could amplify multiple endogenous neuroprotective, pro-cognitive, anti-inflammatory and anti-nociceptive cholinergic pathways to offset cholinergic hypofunction and generate therapeutic efficacy by targeting only a single player: i.e., nAChRs activated by endogenous cholinergic tone. In this article, I review the concept of allosteric modulation and current trends in therapeutic applications of nicotinic PAMs.
authors.affiliation: University of North Texas Health Science Center, Institute for Healthy Aging, Center for Neuroscience Discovery, Fort Worth, TX 76107. Victor.Uteshev@unthsc.edu.
authors.forename: Victor V
authors.initials: VV
authors.lastname: Uteshev
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D008024:Ligands; D018696:Neuroprotective Agents; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic