Porel Pratyush, Hunjan Garry, Singh Shamsher, Aran Khadga Raj
Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab 142001, India.
Department of Pharmacy Practice, ISF College of Pharmacy, Moga, Punjab 142001, India.
Ageing Res Rev. 2025 Aug 5;112:102854. doi: 10.1016/j.arr.2025.102854.
The renin-angiotensin system (RAS), an important regulator of body fluid and cardiovascular homeostasis, is gradually implicated in the pathogenesis of neurological diseases due to its dysregulation. In addition to their traditional functions, components of the RAS, especially angiotensin-II (Ang-II), enhance neuroinflammation, oxidative stress, and neuronal injury. Ang-II exacerbates blood-brain barrier (BBB) disruption, promotes glial activation, and contributes to neurodegeneration via the Angiotensin type 1 (AT1) receptor (AT1R) and causes neurological diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), Huntington's disease (HD), epilepsy, depression, and anxiety. The angiotensin (1-7) axis mediated by the Mas receptor appears to be neuroprotective, however, as it reverses the negative effects of Ang-II. In experimental models and clinical trials, blocking RAS specifically by angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) has demonstrated promise in reducing neuroinflammation and neuronal damage, especially in stroke and neurodegenerative diseases. In the current era of research, neuropharmacologists have new optimism due to emerging evidence of the promising potential of RAS-modulating drugs, such as ARBs and ACEIs, in the treatment of various neurological diseases. Since RAS imbalance causes neuroinflammation, neuronal damage, and cognitive decline in conditions including AD, PD, and MS, these drugs may offer a new treatment approach. In the current era of neuropharmacology, this technique is novel since it enables more targeted therapies to address the root causes of neurodegeneration. This review explores the molecular pathways of RAS dysregulation in various neurological diseases, highlighting its therapeutic potential and paving the way for future treatment strategies.
肾素-血管紧张素系统（RAS）是体液和心血管稳态的重要调节因子，由于其失调，逐渐被认为与神经疾病的发病机制有关。除了其传统功能外，RAS的组成部分，特别是血管紧张素II（Ang-II），会加剧神经炎症、氧化应激和神经元损伤。Ang-II会加剧血脑屏障（BBB）的破坏，促进胶质细胞活化，并通过1型血管紧张素受体（AT1R）导致神经退行性变，引发诸如阿尔茨海默病（AD）、帕金森病（PD）、多发性硬化症（MS）、亨廷顿舞蹈病（HD）、癫痫、抑郁症和焦虑症等神经疾病。然而，由Mas受体介导的血管紧张素（1-7）轴似乎具有神经保护作用，因为它可以逆转Ang-II的负面影响。在实验模型和临床试验中，通过血管紧张素转换酶抑制剂（ACEIs）或血管紧张素受体阻滞剂（ARBs）特异性阻断RAS，已显示出在减少神经炎症和神经元损伤方面的前景，尤其是在中风和神经退行性疾病中。在当前的研究时代，由于有新的证据表明RAS调节药物（如ARBs和ACEIs）在治疗各种神经疾病方面具有潜在的前景，神经药理学家有了新的乐观态度。由于RAS失衡会在包括AD、PD和MS在内的疾病中导致神经炎症、神经元损伤和认知衰退，这些药物可能提供一种新的治疗方法。在当前的神经药理学时代，这项技术是新颖的，因为它能够实现更有针对性的治疗，以解决神经退行性变的根本原因。本综述探讨了RAS在各种神经疾病中失调的分子途径，突出了其治疗潜力，并为未来的治疗策略铺平了道路。
