Jimenez-Moreno Natalia, Lane Jon D
Edinburgh Cancer Research UK Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XR, UK.
Cell Biology Laboratories, School of Biochemistry, University of Bristol, Bristol BS8 1TD, UK.
Oxid Med Cell Longev. 2020 Nov 10;2020:8865611. doi: 10.1155/2020/8865611. eCollection 2020.
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated primarily from endogenous biochemical reactions in mitochondria, endoplasmic reticulum (ER), and peroxisomes. Typically, ROS/RNS correlate with oxidative damage and cell death; however, free radicals are also crucial for normal cellular functions, including supporting neuronal homeostasis. ROS/RNS levels influence and are influenced by antioxidant systems, including the catabolic autophagy pathways. Autophagy is an intracellular lysosomal degradation process by which invasive, damaged, or redundant cytoplasmic components, including microorganisms and defunct organelles, are removed to maintain cellular homeostasis. This process is particularly important in neurons that are required to cope with prolonged and sustained operational stress. Consequently, autophagy is a primary line of protection against neurodegenerative diseases. Parkinson's is caused by the loss of midbrain dopaminergic neurons (mDANs), resulting in progressive disruption of the nigrostriatal pathway, leading to motor, behavioural, and cognitive impairments. Mitochondrial dysfunction, with associated increases in oxidative stress, and declining proteostasis control, are key contributors during mDAN demise in Parkinson's. In this review, we analyse the crosstalk between autophagy and redoxtasis, including the molecular mechanisms involved and the detrimental effect of an imbalance in the pathogenesis of Parkinson's.
活性氧（ROS）和活性氮（RNS）主要由线粒体、内质网（ER）和过氧化物酶体中的内源性生化反应产生。通常，ROS/RNS与氧化损伤和细胞死亡相关；然而，自由基对于正常细胞功能也至关重要，包括维持神经元内环境稳定。ROS/RNS水平影响抗氧化系统，同时也受到抗氧化系统的影响，这些抗氧化系统包括分解代谢自噬途径。自噬是一种细胞内溶酶体降解过程，通过该过程可清除侵入性、受损或多余的细胞质成分，包括微生物和功能失调的细胞器，以维持细胞内环境稳定。这一过程在需要应对长期持续工作压力的神经元中尤为重要。因此，自噬是预防神经退行性疾病的主要防线。帕金森病是由中脑多巴胺能神经元（mDANs）丧失所致，导致黑质纹状体通路逐渐受损，进而引起运动、行为和认知障碍。线粒体功能障碍以及相关的氧化应激增加和蛋白质稳态控制能力下降，是帕金森病中脑多巴胺能神经元死亡的关键因素。在本综述中，我们分析了自噬与氧化还原平衡之间的相互作用，包括其中涉及的分子机制以及帕金森病发病机制中失衡所产生的有害影响。
