Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.
Med Res Rev. 2021 Mar;41(2):770-784. doi: 10.1002/med.21712. Epub 2020 Jul 13.
The world's population aging progression renders age-related neurodegenerative diseases to be one of the biggest unsolved problems of modern society. Despite the progress in studying the development of pathology, finding ways for modifying neurodegenerative disorders remains a high priority. One common feature of neurodegenerative diseases is mitochondrial dysfunction and overproduction of reactive oxygen species, resulting in oxidative stress. Although lipid peroxidation is one of the markers for oxidative stress, it also plays an important role in cell physiology, including activation of phospholipases and stimulation of signaling cascades. Excessive lipid peroxidation is a hallmark for most neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and many other neurological conditions. The products of lipid peroxidation have been shown to be the trigger for necrotic, apoptotic, and more specifically for oxidative stress-related, that is, ferroptosis and neuronal cell death. Here we discuss the involvement of lipid peroxidation in the mechanism of neuronal loss and some novel therapeutic directions to oppose it.
世界人口老龄化进程使得与年龄相关的神经退行性疾病成为现代社会尚未解决的最大问题之一。尽管在研究病理学发展方面取得了进展，但寻找改善神经退行性疾病的方法仍然是当务之急。神经退行性疾病的一个共同特征是线粒体功能障碍和活性氧物质的过度产生，导致氧化应激。虽然脂质过氧化是氧化应激的标志物之一，但它在细胞生理学中也起着重要作用，包括激活磷脂酶和刺激信号级联反应。过度的脂质过氧化是大多数神经退行性疾病的标志，包括阿尔茨海默病、帕金森病、肌萎缩侧索硬化症和许多其他神经疾病。脂质过氧化的产物已被证明是触发坏死、凋亡，更具体地说是与氧化应激相关的铁死亡和神经元细胞死亡的触发因素。在这里，我们讨论了脂质过氧化在神经元丧失机制中的作用以及一些反对它的新的治疗方向。
