Paladino Simona, Conte Andrea, Caggiano Rocco, Pierantoni Giovanna Maria, Faraonio Raffaella
Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
CEINGE-Biotecnologie Avanzate s.c.a.r.l, Naples, Italy.
Cell Physiol Biochem. 2018;47(5):1951-1976. doi: 10.1159/000491465. Epub 2018 Jul 3.
A general hallmark of neurological diseases is the loss of redox homeostasis that triggers oxidative damages to biomolecules compromising neuronal function. Under physiological conditions the steady-state concentrations of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are finely regulated for proper cellular functions. Reduced surveillance of endogenous antioxidant defenses and/or increased ROS/RNS production leads to oxidative stress with consequent alteration of physiological processes. Neuronal cells are particularly susceptible to ROS/RNS due to their biochemical composition. Overwhelming evidences indicate that nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-linked pathways are involved in protective mechanisms against oxidative stress by regulating antioxidant and phase II detoxifying genes. As such, Nrf2 deregulation has been linked to both aging and pathogenesis of many human chronic diseases, including neurodegenerative ones such as Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. Nrf2 activity is tightly regulated by a fine balance between positive and negative modulators. A better understanding of the regulatory mechanisms underlying Nrf2 activity could help to develop novel therapeutic interventions to prevent, slow down or possibly reverse various pathological states. To this end, microRNAs (miRs) are attractive candidates because they are linked to intracellular redox status being regulated and, post-transcriptionally, regulating key components of ROS/RNS pathways, including Nrf2.
神经疾病的一个普遍特征是氧化还原稳态的丧失，这会引发对生物分子的氧化损伤，进而损害神经元功能。在生理条件下，活性氧（ROS）和活性氮（RNS）的稳态浓度受到精确调节，以实现正常的细胞功能。内源性抗氧化防御的监测减少和/或ROS/RNS生成增加会导致氧化应激，从而改变生理过程。由于神经元细胞的生化组成，它们对ROS/RNS特别敏感。大量证据表明，核因子（红细胞衍生2）样2（Nrf2）相关途径通过调节抗氧化剂和II期解毒基因参与了对抗氧化应激的保护机制。因此，Nrf2失调与衰老以及许多人类慢性疾病的发病机制有关，包括帕金森病、阿尔茨海默病和肌萎缩侧索硬化症等神经退行性疾病。Nrf2的活性受到正负调节剂之间精细平衡的严格调控。更好地理解Nrf2活性的调控机制有助于开发新的治疗干预措施，以预防、减缓或可能逆转各种病理状态。为此，微小RNA（miRs）是有吸引力的候选者，因为它们与细胞内氧化还原状态相关，并且在转录后调节ROS/RNS途径的关键成分，包括Nrf2。
