The potential roles of nicotinic acetylcholine receptors in the pathogenesis of multiple sclerosis: A comprehensive review.

Multiple sclerosis (MS) is a chronic immune-mediated disorder of the central nervous system characterized by inflammation, demyelination, and neurodegeneration. Growing evidence suggests that nicotinic acetylcholine receptors (nAChRs), key components of the cholinergic system, play an important role in regulating immune responses and neuroinflammation. In the present review, we summarize and critically evaluate experimental and clinical evidence supporting the involvement of nAChRs in MS pathogenesis. Particular emphasis is placed on receptor subtype-specific effects, including the anti-inflammatory and immunomodulatory properties of α7-containing nAChRs and the emerging roles of α9 and α10 subunits. We also discuss the complex relationship between smoking, nicotine exposure, and MS progression, highlighting the divergent effects of pure nicotine versus other tobacco smoke constituents. Understanding the mechanisms by which nAChRs influence immune cell function, cytokine production, and neurodegeneration may provide novel therapeutic insights and identify new molecular targets for MS treatment.