The Role of α7-Nicotinic Acetylcholine Receptors in the Pathophysiology and Treatment of Parkinson's Disease

The alpha 7 nicotinic acetylcholine receptor (alpha 7-nAChR) is a pivotal regulator of neurotransmission, neuroprotection, and immune modulation in the central nervous system. This review explores its structural and functional attributes, highlighting its therapeutic potential in neurodegenerative disorders, particularly Parkinson's disease (PD). alpha 7-nAChRs mediate synaptic plasticity, modulate inflammatory responses, and influence dopamine release, positioning them as a promising pharmacological target. Positive allosteric modulators (PAMs) enhance alpha 7-nAChR activity mainly by reducing desensitization, offering a superior therapeutic approach compared with direct agonists. Emerging preclinical studies suggest that alpha 7-nAChR activation mitigates dopaminergic neurodegeneration, improves L-dopa-induced dyskinesia, and reduces neuroinflammation. Despite promising findings, clinical trials have yielded mixed results, necessitating further research into optimizing alpha 7-targeted therapies. This review underscores the significance of alpha 7-nAChRs in PD pathophysiology and highlights future directions for their translational potential in neuroprotection and symptomatic relief.