摘要
线粒体氧化应激是引起和加速阿尔茨海默病的重要原因,其会诱导β淀粉样蛋白产生,上调磷酸化tau蛋白的表达,并引发脂质、蛋白质及线粒体脱氧核糖核酸的氧化损伤。其中中枢神经元因需氧量大、富含不饱和脂肪酸,而抗氧化酶缺乏,相较于非神经元细胞对氧化应激更为敏感。本综述以此为切入点,介绍线粒体氧化应激产生的原因,并分析线粒体氧化应激在阿尔茨海默病发病机制中的重要作用。同时重点阐述以神经元线粒体氧化应激为靶点的药物递送系统设计及干预策略,旨在为阿尔茨海默病的防治提供新思路。
Mitochondrial oxidative stress has been recognized as a preliminary and critical factor that aggravates the pathological cascade of Alzheimer’s disease, which induces the production of β-amyloid protein,upregulates the expression of phosphorylated tau protein and triggers oxidative damage to lipids, proteins and mitochondrial deoxyribonucleic acid. Central neurons are more vulnerable to oxidative stress than non-neuronal cells due to their high oxygen demand, abundant unsaturated fatty acids and antioxidant enzymes deficiency. On this account, this review introduces the causes of mitochondrial oxidative stress, and analyzes the important role of mitochondrial oxidative stress in the pathogenesis of Alzheimer’s disease. Meanwhile, the review focuses on the design and intervention strategies of drug delivery systems targeting mitochondrial oxidative stress in neurons,aiming to provide new ideas for the prevention and treatment of Alzheimer’s disease.
作者
周玲玲
钱康
杨鹏
张奇志
ZHOU Ling-ling;QIAN Kang;YANG Peng;ZHANG Qi-zhi(Key Laboratory of Smart Drug Delivery of the Ministry of Education,School of Pharmacy,Hehai University,Shanghai 201203,China)
出处
《药学学报》
CAS
CSCD
北大核心
2022年第6期1630-1640,共11页
Acta Pharmaceutica Sinica
基金
国家自然科学基金资助项目(82073780)。
