Department of Pharmacy, Southeast University, Dhaka, Bangladesh.
Pharmakon Neuroscience Research Network, Dhaka, Bangladesh.
IUBMB Life. 2020 Sep;72(9):1843-1855. doi: 10.1002/iub.2324. Epub 2020 May 30.
Age-related cognitive failure is a main devastating incident affecting even healthy people. Alzheimer's disease (AD) is the utmost common form of dementia among the geriatric community. In the pathogenesis of AD, cerebrovascular dysfunction is revealed before the beginning of the cognitive decline. Mounting proof shows a precarious impact of cerebrovascular dysregulation in the development of AD pathology. Recent studies document that the mammalian target of rapamycin (mTOR) acts as a crucial effector of cerebrovascular dysregulation in AD. The mTOR contributes to brain vascular dysfunction and subsequence cerebral blood flow deficits as well as cognitive impairment. Furthermore, mTOR causes the blood-brain barrier (BBB) breakdown in AD models. Inhibition of mTOR hyperactivity protects the BBB integrity in AD. Furthermore, mTOR drives cognitive defect and cerebrovascular dysfunction, which are greatly prevalent in AD, but the central molecular mechanisms underlying these alterations are obscure. This review represents the crucial and current research findings regarding the role of mTOR signaling in cognitive aging and cerebrovascular dysfunction in the pathogenesis of AD.
与年龄相关的认知功能障碍是影响健康人群的主要灾难性事件。阿尔茨海默病（AD）是老年人群中最常见的痴呆形式。在 AD 的发病机制中，脑血管功能障碍在认知能力下降之前就已经显现出来。越来越多的证据表明，脑血管调节失常在 AD 病理发展中具有潜在的影响。最近的研究表明，雷帕霉素靶蛋白（mTOR）是 AD 中脑血管调节失常的关键效应因子。mTOR 导致脑血管功能障碍和随后的脑血流不足以及认知障碍。此外，mTOR 导致 AD 模型中的血脑屏障（BBB）破裂。mTOR 活性的抑制可保护 AD 中的 BBB 完整性。此外，mTOR 导致 AD 中普遍存在的认知缺陷和脑血管功能障碍，但这些改变的核心分子机制尚不清楚。本综述介绍了 mTOR 信号在 AD 发病机制中对认知衰老和脑血管功能障碍的重要和最新研究结果。
