Murat Oz , Lina Al Kury , Bassem Sadek , Mohamed Omer Mahgoub
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引用次数: 0
摘要
尸检研究发现,自闭症谱系障碍(ASD)患者的大脑表现出胆碱能系统各种成分的异常,包括胆碱能受体、突起和细胞核。15q13.3区域包含编码α7-nACh受体的基因CHRNA7,该区域的缺失与包括ASD在内的多种神经发育障碍有关。此外,以往的研究还报道了α7-nACh 受体参与已知在 ASD 病理生理学中发挥作用的生物学现象,如认知功能、学习、记忆、神经炎症和氧化应激,以及神经元回路中的兴奋-抑制平衡和母体免疫激活。此外,不断发展的临床前和临床文献支持使用选择性胆碱能化合物,尤其是针对α7-nACh受体亚型的胆碱能化合物来治疗ASD可能带来的治疗益处。本研究回顾了以往有关 nACh 受体参与 ASD 病理生理学的文献,并重点关注作为潜在治疗靶点的 α7-nACh 受体。
The role of nicotinic acetylcholine receptors in the pathophysiology and pharmacotherapy of autism spectrum disorder: Focus on α7 nicotinic receptors
Postmortem studies have revealed that brains of individuals with autism spectrum disorder (ASD) exhibit abnormalities in various components of the cholinergic system including cholinergic receptors, projections, and nuclei. Deletions in the 15q13.3 region which encompasses CHRNA7, the gene that encodes the α7-nACh receptor, have been linked to various neurodevelopmental disorders, including ASD. In addition, the involvement of α7-nACh receptors in biological phenomena known to play a role in the pathophysiology of ASD such as cognitive functions, learning, memory, neuroinflammation, and oxidative stress, as well as the excitation-inhibition balance in neuronal circuits and maternal immune activation have been reported in previous studies. Furthermore, evolving preclinical and clinical literature supports the potential therapeutic benefits of using selectively acting cholinergic compounds, particularly those targeting the α7-nACh receptor subtype, in the treatment of ASD. This study reviews the previous literature on the involvement of nACh receptors in the pathophysiology of ASD and focuses on the α7-nACh receptor as a potential therapeutic target.