Instituto de Investigación Sanitaria, Hospital Universitario de la Princesa, 28006 Madrid, Spain; Instituto Teófilo Hernando, Departamento de Farmacología y Terapéutica, Facultad de Medicina, UAM, 28029 Madrid, Spain.
Instituto de Investigación Sanitaria, Hospital Universitario de la Princesa, 28006 Madrid, Spain; Instituto Teófilo Hernando, Departamento de Farmacología y Terapéutica, Facultad de Medicina, UAM, 28029 Madrid, Spain.
Pharmacol Ther. 2016 Jan;157:84-104. doi: 10.1016/j.pharmthera.2015.11.003. Epub 2015 Nov 23.
Neurodegenerative diseases (NDDs) are predicted to be the biggest health concern in this century and the second leading cause of death by 2050. The main risk factor of these diseases is aging, and as the aging population in Western societies is increasing, the prevalence of these diseases is augmenting exponentially. Despite the great efforts to find a cure, current treatments remain ineffective or have low efficacy. Increasing lines of evidence point to exacerbated oxidative stress, mitochondrial dysfunction and chronic neuroinflammation as common pathological mechanisms underlying neurodegeneration. We will address the role of the nuclear factor E2-related factor 2 (Nrf2) as a potential target for the treatment of NDDs. The Nrf2-ARE pathway is an intrinsic mechanism of defence against oxidative stress. Nrf2 is a transcription factor that induces the expression of a great number of cytoprotective and detoxificant genes. There are many evidences that highlight the protective role of the Nrf2-ARE pathway in neurodegenerative conditions, as it reduces oxidative stress and neuroinflammation. Therefore, the Nrf2 pathway is being increasingly considered a therapeutic target for NDDs. Herein we will review the deregulation of the Nrf2 pathway in different NDDs and the recent studies with Nrf2 inducers as "proof-of-concept" for the treatment of those devastating pathologies.
神经退行性疾病（NDDs）预计将成为本世纪最大的健康关注点，并将成为 2050 年的第二大死亡原因。这些疾病的主要风险因素是衰老，随着西方社会人口老龄化的增加，这些疾病的患病率呈指数级增长。尽管人们付出了巨大的努力来寻找治疗方法，但目前的治疗方法仍然无效或疗效低。越来越多的证据表明，氧化应激加剧、线粒体功能障碍和慢性神经炎症是神经退行性变的共同病理机制。我们将讨论核因子 E2 相关因子 2（Nrf2）作为治疗 NDDs 的潜在靶点的作用。Nrf2-ARE 途径是对抗氧化应激的内在防御机制。Nrf2 是一种转录因子，可诱导大量细胞保护和解毒基因的表达。有许多证据表明，Nrf2-ARE 途径在神经退行性疾病中具有保护作用，因为它可以减轻氧化应激和神经炎症。因此，Nrf2 途径正越来越被认为是治疗 NDDs 的一个治疗靶点。本文综述了不同 NDDs 中 Nrf2 途径的失调以及 Nrf2 诱导剂的最新研究，作为治疗这些破坏性疾病的“概念验证”。
