Jalaiei Abbas, Asadi Mohammad Reza, Daneshmandpour Yousef, Rezazadeh Maryam, Ghafouri-Fard Soudeh
Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
J Neurochem. 2025 Jan;169(1):e16200. doi: 10.1111/jnc.16200. Epub 2024 Aug 28.
The α4β2 nAChRs are crucial ion channels that control neurotransmitter release and play a role in various physiologic and pathologic processes. CHRNA4 encodes the α4-nAChRs, while CHRNB2 encodes the β2-nAChRs. Recent studies have found different variants of α4β2-nAChRs in individuals with conditions such as AD, ADHD, ALS, PD, and brain abnormalities. We conducted a scoping review following a six-stage methodology structure and adhering to PRISMA guidelines. We systematically reviewed articles using relevant keywords up to October 2, 2023. In this summary, we cover the clinical symptoms reported, the genes and protein structure of CHRNA4 and CHRNB2, mutations in these genes, inheritance patterns, the functional impact of mutations and polymorphisms in CHRNA4 and CHRNB2, and the epidemiology of these diseases. Recent research indicates that nAChRs may play a significant role in neurodegenerative disorders, possibly impacting neuronal function through yet undiscovered regulatory pathways. Studying how nAChRs interact with disease-related aggregates in neurodegenerative conditions may lead to new treatment options for these disorders.
α4β2烟碱型乙酰胆碱受体是控制神经递质释放的关键离子通道，在各种生理和病理过程中发挥作用。CHRNA4编码α4烟碱型乙酰胆碱受体，而CHRNB2编码β2烟碱型乙酰胆碱受体。最近的研究发现，在患有阿尔茨海默病（AD）、注意力缺陷多动障碍（ADHD）、肌萎缩侧索硬化症（ALS）、帕金森病（PD）和脑异常等疾病的个体中存在α4β2烟碱型乙酰胆碱受体的不同变体。我们按照六阶段方法结构并遵循PRISMA指南进行了一项范围综述。我们使用相关关键词系统地检索了截至2023年10月2日的文章。在本综述中，我们涵盖了所报告的临床症状、CHRNA4和CHRNB2的基因和蛋白质结构、这些基因中的突变、遗传模式、CHRNA4和CHRNB2中突变和多态性的功能影响以及这些疾病的流行病学。最近的研究表明，烟碱型乙酰胆碱受体可能在神经退行性疾病中起重要作用，可能通过尚未发现的调节途径影响神经元功能。研究烟碱型乙酰胆碱受体在神经退行性疾病中如何与疾病相关聚集体相互作用，可能会为这些疾病带来新的治疗选择。
