Singh Sushma, Agrawal Neetu, Goyal Ahsas
Institute of Pharmaceutical Research, GLA University, Mathura 281406, UP, India.
Pharmacy College, Azamgarh- 276128, UP, India.
CNS Neurol Disord Drug Targets. 2024;23(3):384-394. doi: 10.2174/1871527322666230627123426.
Alzheimer's disease (AD) is a neurodegenerative disorder affecting millions worldwide. One of the leading hypotheses for the underlying cause of AD is a reduction in nicotinic receptor levels in the brain. Among the nicotinic receptors, the alpha-7-nicotinic acetylcholine receptor (α7nAChR) has received particular attention due to its involvement in cognitive function.α7nAChR is a ligand-gated ion channel that is primarily found in the hippocampus and prefrontal cortex, areas of the brain responsible for learning, memory, and attention. Studies have shown that α7nAChR dysfunction is a key contributor to the pathogenesis of AD. The receptor is involved in regulating amyloidbeta (Aβ) production, a hallmark of AD pathology. Many drugs have been investigated as α7nAChR agonists or allosteric modulators to improve cognitive deficits in AD. Clinical studies have shown promising results with α7nAChR agonists, including improved memory and cognitive function. Although several studies have shown the significance of the α7 nAChR in AD, little is known about its function in AD pathogenesis. As a result, in this review, we have outlined the basic information of the α7 nAChR's structure, functions, cellular responses to its activation, and its role in AD's pathogenesis.
阿尔茨海默病(AD)是一种影响全球数百万人的神经退行性疾病。关于AD潜在病因的主要假说之一是大脑中烟碱受体水平降低。在烟碱受体中,α7烟碱型乙酰胆碱受体(α7nAChR)因其与认知功能有关而受到特别关注。α7nAChR是一种配体门控离子通道,主要存在于海马体和前额叶皮质,这两个脑区负责学习、记忆和注意力。研究表明,α7nAChR功能障碍是AD发病机制的关键因素。该受体参与调节淀粉样β蛋白(Aβ)的产生,而Aβ是AD病理学的一个标志。许多药物已被研究作为α7nAChR激动剂或变构调节剂,以改善AD患者的认知缺陷。临床研究显示,α7nAChR激动剂取得了令人鼓舞的结果,包括改善记忆和认知功能。尽管多项研究已表明α7nAChR在AD中的重要性,但其在AD发病机制中的功能仍知之甚少。因此,在本综述中,我们概述了α7nAChR的结构、功能、细胞对其激活的反应及其在AD发病机制中的作用的基本信息。