鞘脂代谢在神经退行性变中的作用。
Role of sphingolipid metabolism in neurodegeneration.
机构信息
KACST-BWH Center of Excellence for Biomedicine, Joint Centers of Excellence Program, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia.
Developmental Medicine Department, King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.
出版信息
J Neurochem. 2021 Jul;158(1):25-35. doi: 10.1111/jnc.15044. Epub 2020 Jul 3.
Sphingolipids are a class of lipids highly enriched in the central nervous system (CNS), which shows great diversity and complexity, and has been implicated in CNS development and function. Alterations in sphingolipid metabolism have been described in multiple diseases, including those affecting the central nervous system (CNS). In this review, we discuss the role of sphingolipid metabolism in neurodegeneration, evaluating its direct roles in neuron development and health, and also in the induction of neurotoxic activities in CNS-resident astrocytes and microglia in the context of neurologic diseases such as multiple sclerosis and Alzheimer's disease. Finally, we focus on the metabolism of gangliosides and sphingosine-1-phosphate, its contribution to the pathogenesis of neurologic diseases, and its potential as a candidate target for the therapeutic modulation of neurodegeneration.
鞘脂类是高度富集在中枢神经系统（CNS）中的一类脂质，具有极大的多样性和复杂性，并且与 CNS 的发育和功能有关。鞘脂代谢的改变在多种疾病中都有描述，包括影响中枢神经系统（CNS）的疾病。在这篇综述中，我们讨论了鞘脂代谢在神经退行性变中的作用，评估了其在神经元发育和健康中的直接作用，以及在多发性硬化症和阿尔茨海默病等神经疾病中，诱导中枢神经系统驻留的星形胶质细胞和小胶质细胞产生神经毒性活性的作用。最后，我们重点讨论了神经节苷脂和鞘氨醇 1-磷酸的代谢，及其对神经疾病发病机制的贡献，以及作为神经退行性病变治疗调节的候选靶点的潜力。
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