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.

Figure 1

Relationship of 7 nAChRs to anti-apoptotic and anti-inflammatory pathways. Schematic showing α7 nAChR-mediated activation of JAK2 and cross-talk mechanisms between α7 nAChRs and β-amyloid-activated pathways. α7-mediated neuroprotection via the JAK2 pathway intersects with the anti-inflammatory pathway mediated through STAT3/NF-κB. Abbreviations: Akt (protein kinase B); Bcl-2 (B cell lymphoma 2 protein); IκB (Inhibitor kappa B); JAK2 (Janus kinase 2); NF-κB (nuclear factor kappa B and transcription factor complex); mTOR: mammalian target of rapamycin (kinase); STAT3 (Signal Transducer and Activator of Transcription3). PARP: Poly (ADP-ribose) polymerase.