Brain Renin-Angiotensin System as Novel and Potential Therapeutic Target for Alzheimer's Disease.
Brain Renin-Angiotensin System as Novel and Potential Therapeutic Target for Alzheimer's Disease.
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DOI：
10.3390/ijms221810139
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发表时间：
2021-09-20
影响因子：
5.6
通讯作者：
Maioli S
中科院分区：
文献类型：
--
作者：
Loera-Valencia R;Eroli F;Garcia-Ptacek S;Maioli S
脑内肾素-血管紧张素系统（RAS）的激活在认知的病理生理学中起着关键作用。虽然之前在高血压的背景下研究了脑RAS，但对其与神经元功能及其调节相关的作用和调节知之甚少。充足的血液流向大脑以及代谢副产物的适当清除在神经退行性疾病如阿尔茨海默病（AD）的存在下变得至关重要。RAS抑制（RASi）药物可以进入中枢神经系统，在改善AD患者的认知方面产生了不明确的结果。因此，在临床试验中仅考虑一种RASi疗法来改变AD。此外，非遗传因素如高胆固醇血症在AD的病理生理学中的作用在很大程度上仍然没有表征，即使有证据表明它可以导致动物模型中RAS和认知的改变。在这里，我们修订了大脑RAS在认知和AD发病机制中的功能的证据，并总结了将其与高胆固醇血症和其他危险因素联系起来的证据。我们回顾了现有的RASi治疗药物，并展示了对新型药物的研究，包括小分子和纳米递送策略，这些策略可以以潜在的高特异性靶向大脑RAS。我们希望对大脑RAS功能和调节的进一步研究将导致最终改善AD神经退行性变的创新疗法。
The activation of the brain renin-angiotensin system (RAS) plays a pivotal role in the pathophysiology of cognition. While the brain RAS has been studied before in the context of hypertension, little is known about its role and regulation in relation to neuronal function and its modulation. Adequate blood flow to the brain as well as proper clearing of metabolic byproducts become crucial in the presence of neurodegenerative disorders such as Alzheimer’s disease (AD). RAS inhibition (RASi) drugs that can cross into the central nervous system have yielded unclear results in improving cognition in AD patients. Consequently, only one RASi therapy is under consideration in clinical trials to modify AD. Moreover, the role of non-genetic factors such as hypercholesterolemia in the pathophysiology of AD remains largely uncharacterized, even when evidence exists that it can lead to alteration of the RAS and cognition in animal models. Here we revise the evidence for the function of the brain RAS in cognition and AD pathogenesis and summarize the evidence that links it to hypercholesterolemia and other risk factors. We review existent medications for RASi therapy and show research on novel drugs, including small molecules and nanodelivery strategies that can target the brain RAS with potential high specificity. We hope that further research into the brain RAS function and modulation will lead to innovative therapies that can finally improve AD neurodegeneration.
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影响因子：
16.6
作者：
Hablitz, Lauren M.;Pla, Virginia;Nedergaard, Maiken
通讯作者：
Nedergaard, Maiken
影响因子：
--
作者：
Craft, Suzanne
通讯作者：
Craft, Suzanne
DOI：
10.1073/pnas.1914017117
发表时间：
2020-01-07
影响因子：
11.1
作者：
Cai, Xuezhu;Qiao, Ju;Ferris, Craig F.
通讯作者：
Ferris, Craig F.
执行轻度认知障碍中的降压治疗和脑血流动力学：试点随机临床试验的结果。
影响因子：
6.3
作者：
Hajjar I;Hart M;Chen YL;Mack W;Novak V;C Chui H;Lipsitz L
通讯作者：
Lipsitz L
DOI：
10.1093/brain/awv384
发表时间：
2016-03
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Boussicault L;Alves S;Lamazière A;Planques A;Heck N;Moumné L;Despres G;Bolte S;Hu A;Pagès C;Galvan L;Piguet F;Aubourg P;Cartier N;Caboche J;Betuing S
通讯作者：
Betuing S