Deciphering lipid dysregulation in ALS:from mechanisms to translational medicine  

作　　者：Ira Agrawal Yong Shan Lim Shi-Yan Ng Shuo-Chien Ling 

机构地区：[1]Department of Physiology,Yong Loo Lin School of Medicine,National University of Singapore,Tahir Foundation Building,MD1,16-03-H,12 Science Drive 2,Singapore 117549,Singapore [2]Healthy Longevity Translational Research Programme,Yong Loo Lin School of Medicine,National University of Singapore,Singapore,Singapore [3]Institute of Molecular and Cell Biology,A*STAR Research Entities,Singapore,Singapore [4]Program in Neuroscience and Behavior Disorders,Duke-National University of Singapore Medical School,Singapore,Singapore.

出　　处：《Translational Neurodegeneration》2022年第1期192-218,共27页转化神经变性病（英文）

基　　金：National Medical Research Council(NMRC/OFIRG/0042/2017);National Research Foundation(NRF2019-NRF-ISF003-3221);Ministry of Education(MOE-T2EP30220-0029),Singapore to S.-C.L.

摘　　要：Lipids,defined by low solubility in water and high solubility in nonpolar solvents,can be classified into fatty acids,glycerolipids,glycerophospholipids,sphingolipids,and sterols.Lipids not only regulate integrity and fluidity of biologi-cal membranes,but also serve as energy storage and bioactive molecules for signaling.Causal mutations in SPTLC1(serine palmitoyltransferase long chain subunit 1)gene within the lipogenic pathway have been identified in amyo-trophic lateral sclerosis(ALS),a paralytic and fatal motor neuron disease.Furthermore,lipid dysmetabolism within the central nervous system and circulation is associated with ALS.Here,we aim to delineate the diverse roles of different lipid classes and understand how lipid dysmetabolism may contribute to ALS pathogenesis.Among the different lipids,accumulation of ceramides,arachidonic acid,and lysophosphatidylcholine is commonly emerging as detri-mental to motor neurons.We end with exploring the potential ALS therapeutics by reducing these toxic lipids.

关 键 词：Amyotrophic lateral sclerosis SPHINGOLIPIDS TRIGLYCERIDES Phospholipids Cholesterol esters Fatty acids CERAMIDES Arachidonic acid LYSOPHOSPHATIDYLCHOLINE EICOSANOIDS 

分 类 号：R746.4[医药卫生—神经病学与精神病学]