磷脂过氧化:神经退行性疾病“易感”的关键因素

Phospholipid peroxidation:a key factor in"susceptibility"to neurodegenerative diseases

大脑的生化完整性对于维持大脑的正常运转十分重要,氧化损伤是导致大脑生化完整性破坏的重要原因之一。大脑富含磷脂和多不饱和脂肪酸,由于高脂质和高耗氧量的特殊性,大脑比其他器官更容易受到氧化应激的影响,氧化应激诱导的磷脂过氧化是大脑的氧化-抗氧化系统失衡的结果。当抗氧化系统不足以抵御氧化损伤时,神经元膜磷脂易受自由基活性氧的攻击发生磷脂过氧化,进而生成多种毒性氧化产物、细胞膜损伤、线粒体障碍和淀粉样蛋白的急剧累积,且神经元的大多数蛋白和核酸可以被过氧化产物共价修饰,导致蛋白原有功能的丧失,进而引发大脑程序性细胞死亡和神经炎症,最终导致神经退行性疾病的易感性的增加。本文在总结磷脂过氧化机制的基础上,重点综述了磷脂过氧化作为关键因素在神经退行性疾病的发生发展中的特点,为靶向干预磷脂过氧化用于预防神经退行性疾病的潜在策略提供理论依据。

The biochemical integrity of the brain is necessary to maintain normal function.Oxidative damage is one of the mortal important reasons leading to the destruction of this integrity.The nervous system is enriched in phospholipid and polyunsaturated fatty acids(PUFAs).Due to the nature of high oxygen-consumption and rich lipids,brain is particularly vulnerable to oxidative damages.Phospholipid peroxidation is one of the results of imbalance in oxidation-antioxidant system.Once the antioxidant system is insufficient to resist oxidative damage,membrane phospholipids will be prone to free radical attack.Phospholipid peroxidation leads to a variety of toxic oxidation products,including membrane damage,mitochondrial dysfunction,rapid accumulation of amyloid,etc.Multiple proteins and nucleic acids can be covalently modified by peroxidation products,resulting in the loss of the protein functions,which eventually triggers programmed cell death and general neuroinflammation in brain,and ends up with an increased susceptibility to neurodegenerative diseases.Based on the knowledge of mechanisms of phospholipid peroxidation,this review focuses on the characteristics of phospholipid peroxidation as a key factor in the development of neurodegenerative diseases,in order to provide theoretical basis for targeted intervention of phospholipid peroxidation as a potential strategy to prevent neurodegenerative diseases.