Neuronal nicotinic receptors as novel targets for inflammation and neuroprotection: mechanistic considerations and clinical relevance

Abstract

A number of studies have confirmed the potential for neuronal nicotinic acetylcholine receptor (NNR)-mediated neuroprotection and, more recently, its anti-inflammatory effects. The mechanistic overlap between these pathways and the ubiquitous effects observed following diverse insults suggest that NNRs modulate fundamental pathways involved in cell survival. These results have wide-reaching implications for the design of experimental therapeutics that regulate inflammatory and anti-apoptotic responses through NNRs and represent an initial step toward understanding the benefits of novel therapeutic strategies for the management of central nervous system disorders that target neuronal survival and associated inflammatory processes.

Therapeutic Potential ofα7 Nicotinic Acetylcholine Receptors

“…To date there are no approved drugs specific for the treatment of sepsis, a costly illness that is poorly understood (Deutschman and Tracey, 2014). It is known that severe sepsis involves a flood of cytokine production, including TNFa, interleukin-1b, interleukin-10, interferon gamma, and HMGB1 (Bencherif, 2009;Bencherif et al, 2011), in which HMGB1 is a late lethal mediator of sepsis (Kim et al, 2014b). This flood of cytokines involves the participation of intracellular and extracellular "danger signals" that activate inflammasomes to mediate the release of these cytokines and involves both P2X7 receptors and a7 nAChRs (Deutschman and Tracey, 2014).…”

α6β2* and α4β2* Nicotinic Acetylcholine Receptors As Drug Targets for Parkinson's Disease

“…One approach to evaluate a role for nicotine is to investigate its neuroprotective properties against nigrostriatal damage in parkinsonian animal models (Belluardo et al, 2000;O'Neill et al, 2002;Quik et al, 2007b;Picciotto and Zoli, 2008;Bencherif, 2009). A frequently used rat model involves unilateral administration of 6-hydroxydopamine into the striatum, SN pars compacta, or medial forebrain bundle or hemisection of the nigrostriatal dopaminergic pathway (Figs.…”

Nicotine‐mediated neuroprotection of rat spinal networks against excitotoxicity

“…nAChRs are implicated in neuroprotection mechanisms against acute cell distress (Bencherif, ) induced by excitotoxicity, namely a process of over‐activation of glutamate receptors considered as a paradigm of neurodegeneration (Choi, , ). Nicotine‐mediated neuroprotection has been reported in vitro (Garrido, King‐Pospisil, Son, Hennig, & Toborek, ), in vivo (Xue, Liu, Zhang, & Gao, ) and in epidemiological studies (Quik, Perez, & Bordia, ), suggesting potential strategies to contrast neuronal death.…”