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阿尔茨海默病中的去甲肾上腺素:一个新的潜在治疗靶点。

Noradrenaline in Alzheimer's Disease: A New Potential Therapeutic Target.

机构信息

Department of Pharmacology and Toxicology, School of Medicine, Universidad Complutense de Madrid (UCM), Instituto de Investigación Sanitaria Hospital 12 de Octubre (Imas12), Instituto de Investigación Neuroquímica (IUINQ-UCM), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Avda. Complutense s/n, 28040 Madrid, Spain.

Department of Healthcare Surveillance and Bioethics, Section of Pharmacology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.

出版信息

Int J Mol Sci. 2022 May 30;23(11):6143. doi: 10.3390/ijms23116143.

Abstract

A growing body of evidence demonstrates the important role of the noradrenergic system in the pathogenesis of many neurodegenerative processes, especially Alzheimer's disease, due to its ability to control glial activation and chemokine production resulting in anti-inflammatory and neuroprotective effects. Noradrenaline involvement in this disease was first proposed after finding deficits of noradrenergic neurons in the locus coeruleus from Alzheimer's disease patients. Based on this, it has been hypothesized that the early loss of noradrenergic projections and the subsequent reduction of noradrenaline brain levels contribute to cognitive dysfunctions and the progression of neurodegeneration. Several studies have focused on analyzing the role of noradrenaline in the development and progression of Alzheimer's disease. In this review we summarize some of the most relevant data describing the alterations of the noradrenergic system normally occurring in Alzheimer's disease as well as experimental studies in which noradrenaline concentration was modified in order to further analyze how these alterations affect the behavior and viability of different nervous cells. The combination of the different studies here presented suggests that the maintenance of adequate noradrenaline levels in the central nervous system constitutes a key factor of the endogenous defense systems that help prevent or delay the development of Alzheimer's disease. For this reason, the use of noradrenaline modulating drugs is proposed as an interesting alternative therapeutic option for Alzheimer's disease.

摘要

越来越多的证据表明,去甲肾上腺素系统在许多神经退行性过程的发病机制中起着重要作用,特别是在阿尔茨海默病中,因为它能够控制神经胶质细胞的激活和趋化因子的产生,从而产生抗炎和神经保护作用。去甲肾上腺素在这种疾病中的作用最初是在发现阿尔茨海默病患者蓝斑中的去甲肾上腺素神经元缺失后提出的。基于这一点,有人假设,去甲肾上腺素投射的早期丧失和随后脑内去甲肾上腺素水平的降低导致认知功能障碍和神经退行性变的进展。许多研究都集中在分析去甲肾上腺素在阿尔茨海默病的发展和进展中的作用。在这篇综述中,我们总结了一些最相关的数据,描述了阿尔茨海默病中去甲肾上腺素系统通常发生的改变,以及为了进一步分析这些改变如何影响不同神经细胞的行为和活力而改变去甲肾上腺素浓度的实验研究。这里呈现的不同研究的组合表明,维持中枢神经系统中足够的去甲肾上腺素水平是内源性防御系统的关键因素,有助于预防或延缓阿尔茨海默病的发展。因此,使用去甲肾上腺素调节药物被提议作为阿尔茨海默病的一种有趣的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5295/9181823/9316f246a846/ijms-23-06143-g001.jpg

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