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各种认知障碍发病机制中神经元烟碱型乙酰胆碱受体的改变。

Alterations in Neuronal Nicotinic Acetylcholine Receptors in the Pathogenesis of Various Cognitive Impairments.

机构信息

Department of Pathology, The Affiliated Hospital of Guizhou Medical University, Guiyang, P.R. China.

Key Laboratory of Endemic and Ethnic Diseases, Guizhou Medical University, Ministry of Education and Provincial Key Laboratory of Medical Molecular Biology, Guiyang, P.R. China.

出版信息

CNS Neurosci Ther. 2024 Oct;30(10):e70069. doi: 10.1111/cns.70069.

Abstract

Cognitive impairment is a typical symptom of both neurodegenerative and certain other diseases. In connection with these different pathologies, the etiology and neurological and metabolic changes associated with cognitive impairment must differ. Until these characteristics and differences are understood in greater detail, pharmacological treatment of the different forms of cognitive impairment remains suboptimal. Neurotransmitter receptors, including neuronal nicotinic acetylcholine receptors (nAChRs), dopamine receptors, and glutamine receptors, play key roles in the functions and metabolisms of the brain. Among these, the role of nAChRs in the development of cognitive impairment has attracted more and more attention. The present review summarizes what is presently known concerning the structure, distribution, metabolism, and function of nAChRs, as well as their involvement in major cognitive disorders such as Alzheimer's disease, Parkinson's disease, vascular dementia, schizophrenia, and diabetes mellitus. As will be discussed, the relevant scientific literature reveals clearly that the α4β2 and α7 nAChR subtypes and/or subunits of the receptors play major roles in maintaining cognitive function and in neuroprotection of the brain. Accordingly, focusing on these as targets of drug therapy can be expected to lead to breakthroughs in the treatment of cognitive disorders such as AD and schizophrenia.

摘要

认知障碍是神经退行性疾病和某些其他疾病的典型症状。与这些不同的病理相关,认知障碍相关的病因学和神经及代谢变化必须有所不同。在更详细地了解这些特征和差异之前,对不同形式的认知障碍的药物治疗仍然不尽如人意。神经递质受体,包括神经元烟碱型乙酰胆碱受体(nAChRs)、多巴胺受体和谷氨酸受体,在大脑的功能和代谢中发挥关键作用。其中,nAChRs 在认知障碍发展中的作用引起了越来越多的关注。本综述总结了目前已知的 nAChRs 的结构、分布、代谢和功能,以及它们在阿尔茨海默病、帕金森病、血管性痴呆、精神分裂症和糖尿病等主要认知障碍中的作用。正如将讨论的那样,相关科学文献清楚地表明,α4β2 和 α7 nAChR 亚型和/或受体的亚基在维持认知功能和大脑神经保护方面发挥着重要作用。因此,将这些作为药物治疗的靶点有望为治疗阿尔茨海默病和精神分裂症等认知障碍带来突破。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05db/11456617/48138f4e6f39/CNS-30-e70069-g002.jpg

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