PDF(Pubmed)
Abstract：
Parkinson disease (PD) is one of the most common neurodegenerative diseases of the brain. Of note, brain renin-angiotensin system (RAS) is intricate in the PD neuropathology through modulation of oxidative stress, mitochondrial dysfunction and neuroinflammation. Therefore, modulation of brain RAS by angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) may be effective in reducing the risk and PD neuropathology. It has been shown that all components including the peptides and enzymes of the RAS are present in the different brain areas. Brain RAS plays a critical role in the regulation of memory and cognitive function, and in the controlling of central blood pressure. However, exaggerated brain RAS is implicated in the pathogenesis of different neurodegenerative diseases including PD. Two well-known pathways of brain RAS are recognized including; the classical pathway which is mainly mediated by AngII/AT1R has detrimental effects. Conversely, the non-classical pathway which is mostly mediated by ACE2/Ang1-7/MASR and AngII/AT2R has beneficial effects against PD neuropathology. Exaggerated brain RAS affects the viability of dopaminergic neurons. However, the fundamental mechanism of brain RAS in PD neuropathology was not fully elucidated. Consequently, the purpose of this review is to disclose the mechanistic role of RAS in in the pathogenesis of PD. In addition, we try to revise how the ACEIs and ARBs can be developed for therapeutics in PD.
摘要：
帕金森病(PD)是最常见的脑部神经退行性疾病之一。值得注意的是，脑肾素-血管紧张素系统（RAS）是复杂的PD神经病理学通过调节氧化应激，线粒体功能障碍和神经炎症。因此,血管紧张素受体阻滞剂（ARB）和血管紧张素转换酶抑制剂（ACEI）对大脑RAS的调节可能有效降低风险和PD神经病理学。已经显示,包括RAS的肽和酶的所有组分存在于不同的脑区域中。脑RAS在记忆和认知功能的调节中起着至关重要的作用，以及控制中枢血压。然而,夸大的脑RAS与包括PD在内的不同神经退行性疾病的发病机理有关。大脑RAS的两种众所周知的途径被认为包括:主要由AngII/AT1R介导的经典途径具有有害作用。相反，主要由ACE2/Ang1-7/MASR和AngII/AT2R介导的非经典途径对PD神经病理学具有有益作用。夸张的脑RAS影响多巴胺能神经元的活力。然而,脑RAS在PD神经病理学中的基本机制尚未完全阐明。因此,这篇综述的目的是揭示RAS在PD发病机制中的作用。此外,我们试图修改ACEI和ARB如何开发用于PD治疗的方法。
