The Role of α7-Nicotinic Acetylcholine Receptors in the Pathophysiology and Treatment of Parkinson’s Disease
Eslam El Nebrisi, Yosra Lozon, Murat Öz
Abstract
The α7 nicotinic acetylcholine receptor (α7-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). α7-nAChRs mediate synaptic plasticity, modulate inflammatory responses, and influence dopamine release, positioning them as a promising pharmacological target. Positive allosteric modulators (PAMs) enhance α7-nAChR activity mainly by reducing desensitization, offering a superior therapeutic approach compared with direct agonists. Emerging preclinical studies suggest that α7-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 α7-targeted therapies. This review underscores the significance of α7-nAChRs in PD pathophysiology and highlights future directions for their translational potential in neuroprotection and symptomatic relief.