Department of Molecular Pharmacology, The Bruce Rappaport Faculty of Medicine, Israel Institute of Technology-Technion, Haifa, Israel.
Histol Histopathol. 2012 Mar;27(3):263-75. doi: 10.14670/HH-27.263.
Oxidative stress, inflammation and the aggregation of oxidized, misfolded or aberrant proteins in the brain induces deregulations in programmed cell death: apoptosis and autophagy. Apoptosis is one of processes implicated in aging and neurodegenerative pathologies, and for the last decade, has been one of the most studied processes due to its essential role, not only in aging, but also in many neurodegenerative diseases, including Parkinson's, Alzheimer's and Huntington's. However, autophagy being the major intracellular pathway for the degradation and recycling of long-live proteins and organelles is widely involved in the pathogenesis or prevention of many age-related diseases, including neurodegenerative conditions. Recently, autophagy activation has been considered as part of the cellular responses to elevated oxidative stress, eliminating unwanted, damaged and oxidative structures; thus favouring, in this way, the key anti-aging mechanism associated with the caloric restriction. Longevity factors, such as sirtuins, and redox-sensitive transcriptional factors, such as NF-κB and p53, can also regulate basal autophagy in cells, with a direct impact on longevity and the development of inflammation and neurodegeneration. Here, we reviewed the critical changes of autophagy in the aging and neuro-degenerative brain and the role of key regulators of autophagy, which are directly related to oxidative stress, inflammation and longevity pathways.
氧化应激、炎症以及大脑中氧化、错误折叠或异常蛋白质的聚集，会导致程序性细胞死亡（细胞凋亡和自噬）失调。细胞凋亡是与衰老和神经退行性病理相关的过程之一，在过去十年中，由于其在衰老以及许多神经退行性疾病（包括帕金森病、阿尔茨海默病和亨廷顿病）中的重要作用，成为研究最多的过程之一。然而，自噬作为降解和回收长寿蛋白质和细胞器的主要细胞内途径，广泛参与许多与年龄相关的疾病（包括神经退行性疾病）的发病机制或预防。最近，自噬的激活被认为是细胞对氧化应激升高的反应的一部分，消除不需要的、受损的和氧化的结构；从而有利于与热量限制相关的关键抗衰老机制。长寿因子，如沉默信息调节因子 2 相关酶 1 (Sirtuins)，以及氧化还原敏感的转录因子，如核因子-κB (NF-κB) 和 p53，也可以调节细胞中的基础自噬，直接影响寿命以及炎症和神经退行性变的发展。在这里，我们综述了自噬在衰老和神经退行性大脑中的关键变化，以及与氧化应激、炎症和长寿途径直接相关的自噬关键调节因子的作用。
