ElNebrisi Eslam, Lozon Yosra, Oz Murat
Department of Biomedical Sciences, Dubai Medical College for Girls, Dubai Medical University, Dubai 20170, United Arab Emirates.
Department of Pharmaceutical Sciences, Dubai Pharmacy College for Girls, Dubai Medical University, Dubai 20170, United Arab Emirates.
Int J Mol Sci. 2025 Mar 30;26(7):3210. doi: 10.3390/ijms26073210.
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.
α7烟碱型乙酰胆碱受体(α7-nAChR)是中枢神经系统中神经传递、神经保护和免疫调节的关键调节因子。本综述探讨了其结构和功能特性,强调了其在神经退行性疾病,特别是帕金森病(PD)中的治疗潜力。α7-nAChR介导突触可塑性、调节炎症反应并影响多巴胺释放,使其成为一个有前景的药理学靶点。正变构调节剂(PAMs)主要通过减少脱敏来增强α7-nAChR活性,与直接激动剂相比提供了一种更优的治疗方法。新兴的临床前研究表明,α7-nAChR激活可减轻多巴胺能神经变性、改善左旋多巴引起的运动障碍并减少神经炎症。尽管有令人鼓舞的发现,但临床试验结果喜忧参半,需要进一步研究以优化针对α7的治疗方法。本综述强调了α7-nAChR在PD病理生理学中的重要性,并突出了其在神经保护和症状缓解方面转化潜力的未来方向。