Abstract

Alzheimer’s disease (AD) is the most common cause of dementia worldwide that has an increasing impact on aging societies. Besides its critical role in the control of various physiological functions and behavior, brain serotonin (5-HT) system is involved in the regulation of migration, proliferation, differentiation, maturation, and programmed death of neurons. At the same time, a growing body of evidence indicates the involvement of 5-HT neurotransmission in the formation of insoluble aggregates of β-amyloid and tau protein, the main histopathological signs of AD. The review describes the role of various 5-HT receptors and intracellular signaling cascades induced by them in the pathological processes leading to the development of AD, first of all, in protein aggregation. Changes in the functioning of certain types of 5-HT receptors or associated intracellular signaling mediators prevent accumulation of β-amyloid plaques and tau protein neurofibrillary tangles. Based on the experimental data, it can be suggested that the use of 5-HT receptors as new drug targets will not only improve cognitive performance in AD, but will be also important in treating the causes of AD-related dementia.

中文翻译：

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血清素受体作为治疗阿尔茨海默病的潜在靶点

摘要

阿尔茨海默病 (AD) 是全世界痴呆症的最常见原因，对老龄化社会的影响越来越大。脑血清素（5-HT）系统除了在控制各种生理功能和行为中发挥关键作用外，还参与神经元迁移、增殖、分化、成熟和程序性死亡的调节。与此同时，越来越多的证据表明 5-HT 神经传递参与了 β-淀粉样蛋白和 tau 蛋白不溶性聚集体的形成，这是 AD 的主要组织病理学标志。该综述描述了各种 5-HT 受体及其诱导的细胞内信号级联在导致 AD 发展的病理过程中的作用，首先是在蛋白质聚集中的作用。某些类型 5-HT 受体或相关细胞内信号传导介质功能的变化可防止 β-淀粉样斑块和 tau 蛋白神经原纤维缠结的积累。根据实验数据，可以表明使用5-HT受体作为新的药物靶点不仅可以改善AD的认知能力，而且对于治疗AD相关痴呆的病因也很重要。