肾素-血管紧张素系统在神经系统疾病中是敌是友?揭示其作用和治疗潜力

IF 12.4 1区 医学 Q1 CELL BIOLOGY
Pratyush Porel , Garry Hunjan , Shamsher Singh , Khadga Raj Aran
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引用次数: 0

摘要

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,由于其失调而逐渐涉及神经系统疾病的发病机制。除了它们的传统功能外,RAS的成分,特别是血管紧张素- ii (Ang-II),还能增强神经炎症、氧化应激和神经元损伤。Ang-II加剧血脑屏障(BBB)破坏,促进胶质细胞激活,并通过血管紧张素1型(AT1)受体(AT1R)导致神经退行性变,并导致神经系统疾病,如阿尔茨海默病(AD)、帕金森病(PD)、多发性硬化症(MS)、亨廷顿病(HD)、癫痫、抑郁和焦虑。然而,Mas受体介导的血管紧张素(1−7)轴似乎具有神经保护作用,因为它逆转了Ang-II的负面作用。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已被证明在减少神经炎症和神经元损伤,特别是在中风和神经退行性疾病中具有前景。在当前的研究时代,神经药理学家有了新的乐观,因为越来越多的证据表明,ras调节药物,如arb和acei,在治疗各种神经系统疾病方面具有广阔的潜力。由于RAS失衡会导致AD、PD和MS等疾病的神经炎症、神经元损伤和认知能力下降,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,这种技术是新颖的,因为它使更有针对性的治疗来解决神经变性的根本原因。本文综述了多种神经系统疾病中RAS失调的分子途径,强调了其治疗潜力,并为未来的治疗策略铺平了道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Is the renin-angiotensin system a friend or foe in neurological diseases? Unveiling its role and therapeutic potential
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.
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来源期刊
Ageing Research Reviews
Ageing Research Reviews 医学-老年医学
CiteScore
19.80
自引率
2.30%
发文量
216
审稿时长
55 days
期刊介绍: With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends. ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research. The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.
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