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Microglia, which are resident immune cells in the central nervous system (CNS), are key players that maintain brain homeostasis by communicating with other cells, such as astrocytes and immune cells, in or around the CNS. Furthermore, dysfunction of microglia and the immune system of the CNS could lead to chronic neuroinflammation and impairment of protective neuroimmune responses, which have been associated with the pathogenesis of AD and other forms of dementia. In this review, we assemble information regarding genetic evidence, imaging and biofluid biomarkers, and the pathophysiology of AD, especially highlighting bilateral (protective or detrimental) microglial functions, thus connecting neuroimmune dysfunction and AD. We also introduce candidate drugs to target neuroimmune dysfunction in AD. Finally, we discuss future therapeutic precision medicine approaches for AD, which could be achieved by identifying and targeting signals critical for AD pathogenesis through analyses of interactions between genetic risk factors, as well as identifying and modulating disease-relevant immune cell populations.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.5000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Neuroimmune Dysfunction in Alzheimer's Disease and Other Forms of Dementia.\",\"authors\":\"Takuya Yamane, Takeshi Yoshioka, Yusuke Shimo\",\"doi\":\"10.1248/cpb.c23-00464\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Alzheimer's disease (AD) is a common form of dementia. 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引用次数: 0
摘要
阿尔茨海默病(AD)是一种常见的痴呆症。虽然阿尔茨海默病的致病机制尚未完全明了,但淀粉样蛋白β(Aβ)和tau聚集体在脑内的积聚似乎在疾病的发展中起着重要作用。因此,针对 Aβ 和 tau 蛋白的实验和临床研究层出不穷。然而,这些治疗方法并未取得良好的临床效果。此外,最近的研究结果表明,免疫异常也是AD的发病机制之一。一些与免疫和小胶质细胞相关的基因已被确定为该疾病的潜在致病基因。小胶质细胞是中枢神经系统(CNS)中的常驻免疫细胞,是通过与中枢神经系统内或周围的其他细胞(如星形胶质细胞和免疫细胞)交流来维持大脑平衡的关键角色。此外,小胶质细胞和中枢神经系统免疫系统的功能障碍可能会导致慢性神经炎症和保护性神经免疫反应的损害,这与注意力缺失症和其他形式痴呆症的发病机制有关。在这篇综述中,我们汇集了有关遗传学证据、成像和生物流体生物标志物以及 AD 病理生理学的信息,特别强调了小胶质细胞的双边(保护性或有害性)功能,从而将神经免疫功能障碍与 AD 联系起来。我们还介绍了针对 AD 神经免疫功能障碍的候选药物。最后,我们讨论了未来的 AD 精准医学治疗方法,这些方法可以通过分析遗传风险因素之间的相互作用来识别和靶向对 AD 发病至关重要的信号,以及识别和调节与疾病相关的免疫细胞群来实现。
Neuroimmune Dysfunction in Alzheimer's Disease and Other Forms of Dementia.
Alzheimer's disease (AD) is a common form of dementia. Although the causal mechanisms of AD are not fully understood, intracerebral accumulation of amyloid beta (Aβ) and tau aggregates seems to play an important role in disease development. Therefore, numerous experimental and clinical studies targeting the Aβ and tau proteins have been performed. However, these treatments have not achieved good clinical results. Additionally, recent findings have indicated that immune abnormalities contribute to the pathogenesis of AD. Several immune- and microglia-related genes have been identified as putative causative genes for the disease. Microglia, which are resident immune cells in the central nervous system (CNS), are key players that maintain brain homeostasis by communicating with other cells, such as astrocytes and immune cells, in or around the CNS. Furthermore, dysfunction of microglia and the immune system of the CNS could lead to chronic neuroinflammation and impairment of protective neuroimmune responses, which have been associated with the pathogenesis of AD and other forms of dementia. In this review, we assemble information regarding genetic evidence, imaging and biofluid biomarkers, and the pathophysiology of AD, especially highlighting bilateral (protective or detrimental) microglial functions, thus connecting neuroimmune dysfunction and AD. We also introduce candidate drugs to target neuroimmune dysfunction in AD. Finally, we discuss future therapeutic precision medicine approaches for AD, which could be achieved by identifying and targeting signals critical for AD pathogenesis through analyses of interactions between genetic risk factors, as well as identifying and modulating disease-relevant immune cell populations.
期刊介绍:
The CPB covers various chemical topics in the pharmaceutical and health sciences fields dealing with biologically active compounds, natural products, and medicines, while BPB deals with a wide range of biological topics in the pharmaceutical and health sciences fields including scientific research from basic to clinical studies. For details of their respective scopes, please refer to the submission topic categories below.
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