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Brain angiotensin II and angiotensin IV receptors as potential Alzheimer's disease therapeutic targets.
GeroScience ( IF 5.3 ) Pub Date : 2020-07-22 , DOI: 10.1007/s11357-020-00231-y
Jessika Royea 1 , Edith Hamel 1
Affiliation  

Alzheimer’s disease (AD) is a neurodegenerative disorder that is multifactorial in nature. Yet, despite being the most common form of dementia in the elderly, AD’s primary cause remains unknown. As such, there is currently little to offer AD patients as the vast majority of recently tested therapies have either failed in well-controlled clinical trials or inadequately treat AD. Recently, emerging preclinical and clinical evidence has associated the brain renin angiotensin system (RAS) to AD pathology. Accordingly, various components of the brain RAS were shown to be altered in AD patients and mouse models, including the angiotensin II type 1 (AT1R), angiotensin IV receptor (AT4R), and Mas receptors. Collectively, the changes observed within the RAS have been proposed to contribute to many of the neuropathological hallmarks of AD, including the neuronal, cognitive, and vascular dysfunctions. Accumulating evidence has additionally identified antihypertensive medications targeting the RAS, particularly angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs), to delay AD onset and progression. In this review, we will discuss the emergence of the RAS’s involvement in AD and highlight putative mechanisms of action underlying ARB’s beneficial effects that may explain their ability to modify the risk of developing AD or AD progression. The RAS may provide novel molecular targets for recovering memory pathways, cerebrovascular function, and other pathological landmarks of AD.



中文翻译:

脑血管紧张素II和血管紧张素IV受体是潜在的阿尔茨海默氏病治疗靶点。

阿尔茨海默氏病(AD)是一种本质上是多因素的神经退行性疾病。然而,尽管AD是老年人中最常见的痴呆形式,但其主要原因仍是未知的。因此,由于几乎所有最新测试的疗法在控制良好的临床试验中均失败或对AD的治疗不足,因此目前尚无AD患者。最近,新出现的临床前和临床证据已将脑肾素血管紧张素系统(RAS)与AD病理相关。因此,在AD患者和小鼠模型中,大脑RAS的各种成分均发生了变化,包括1型血管紧张素II(AT1R),IV血管紧张素受体(AT4R)和Mas受体。总的来说,已提出在RAS中观察到的变化有助于AD的许多神经病理学特征,包括神经元,认知和血管功能障碍。越来越多的证据还确定了靶向RAS的抗高血压药物,特别是血管紧张素受体阻滞剂(ARB)和血管紧张素转化酶抑制剂(ACEIs),可以延缓AD的发作和发展。在这篇综述中,我们将讨论RAS参与AD的出现,并着重强调ARB有益作用基础的假定作用机制,这可能解释了它们改变发展AD或AD进展风险的能力。RAS可能为恢复AD的记忆通路,脑血管功能和其他病理标志提供新的分子靶标。特别是血管紧张素受体阻滞剂(ARB)和血管紧张素转化酶抑制剂(ACEIs),以延迟AD的发作和进展。在这篇综述中,我们将讨论RAS参与AD的出现,并着重强调ARB有益作用基础的假定作用机制,这可能解释了它们改变发展AD或AD进展风险的能力。RAS可能为恢复AD的记忆通路,脑血管功能和其他病理标志提供新的分子靶标。特别是血管紧张素受体阻滞剂(ARB)和血管紧张素转化酶抑制剂(ACEIs),以延迟AD的发作和进展。在这篇综述中,我们将讨论RAS参与AD的出现,并着重强调ARB有益作用基础的假定作用机制,这可能解释了它们改变发展AD或AD进展风险的能力。RAS可能为恢复AD的记忆通路,脑血管功能和其他病理标志提供新的分子靶标。我们将讨论RAS参与AD的出现,并重点强调ARB有益效应的潜在作用机制,这可能解释了它们改变AD或AD进展风险的能力。RAS可能为恢复AD的记忆通路,脑血管功能和其他病理标志提供新的分子靶标。我们将讨论RAS参与AD的出现,并着重说明ARB有益效应的潜在作用机制,这可能解释了其修饰发展AD或AD进展风险的能力。RAS可能为恢复AD的记忆通路,脑血管功能和其他病理标志提供新的分子靶标。

更新日期:2020-07-24
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