Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, Faculty of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
Mov Disord. 2013 Sep;28(10):1337-42. doi: 10.1002/mds.25614. Epub 2013 Aug 7.
Renin-angiotensin systems are known to act in many tissues, for example, the blood vessel wall or kidney, where a close interaction between angiotensin and dopamine has been demonstrated. Regulatory interactions between the dopaminergic and renin-angiotensin systems have recently been described in the substantia nigra and striatum. In animal models, dopamine depletion induces compensatory overactivation of the local renin-angiotensin system, which primes microglial responses and neuron vulnerability by activating NADPH-oxidase. Hyperactivation of the local renin-angiotensin system exacerbates the inflammatory microglial response, oxidative stress, and dopaminergic degeneration, all of which are inhibited by angiotensin receptor blockers and inhibitors of angiotensin-converting enzymes. In this review we provide evidence suggesting that the renin-angiotensin system may play an important role in dopamine's mediated neuroinflammation and oxidative stress changes in Parkinson's disease. We suggest that manipulating brain angiotensin may constitute an effective neuroprotective strategy for Parkinson's disease.
肾素-血管紧张素系统在许多组织中都有作用，例如血管壁或肾脏，在这些组织中已经证明了血管紧张素和多巴胺之间的密切相互作用。最近在黑质和纹状体中描述了多巴胺能和肾素-血管紧张素系统之间的调节相互作用。在动物模型中，多巴胺耗竭会诱导局部肾素-血管紧张素系统的代偿性过度激活，通过激活 NADPH 氧化酶使小胶质细胞反应和神经元易损性。局部肾素-血管紧张素系统的过度激活加剧了炎症性小胶质细胞反应、氧化应激和多巴胺能退行性变，所有这些都可以被血管紧张素受体阻滞剂和血管紧张素转换酶抑制剂抑制。在这篇综述中，我们提供的证据表明，肾素-血管紧张素系统可能在帕金森病中多巴胺介导的神经炎症和氧化应激变化中发挥重要作用。我们建议，操纵大脑中的血管紧张素可能是帕金森病的一种有效的神经保护策略。
