Cincinnati Children's Hospital Medical Center, Division of Human Genetics, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
Department of Pediatrics, Division of Human Genetics, College of Medicine, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
Int J Mol Sci. 2022 Jan 19;23(3):1089. doi: 10.3390/ijms23031089.
Parkinson's disease (PD) is the second-most common neurodegenerative disease in the world, affecting up to 10 million people. This disease mainly happens due to the loss of dopaminergic neurons accountable for memory and motor function. Partial glucocerebrosidase enzyme deficiency and the resultant excess accumulation of glycosphingolipids and alpha-synuclein (α-syn) aggregation have been linked to predominant risk factors that lead to neurodegeneration and memory and motor defects in PD, with known and unknown causes. An increasing body of evidence uncovers the role of several other lipids and their association with α-syn aggregation, which activates the innate and adaptive immune system and sparks brain inflammation in PD. Here, we review the emerging role of a number of lipids, i.e., triglyceride (TG), diglycerides (DG), glycerophosphoethanolamines (GPE), polyunsaturated fatty acids (PUFA), sphingolipids, gangliosides, glycerophospholipids (GPL), and cholesterols, and their connection with α-syn aggregation as well as the induction of innate and adaptive immune reactions that trigger neuroinflammation in PD.
帕金森病(PD)是世界上第二常见的神经退行性疾病,影响多达 1000 万人。这种疾病主要是由于负责记忆和运动功能的多巴胺能神经元丧失引起的。部分葡萄糖脑苷脂酶缺乏症和由此产生的糖脂和α-突触核蛋白(α-syn)聚集物的过度积累与导致神经退行性变和 PD 中记忆和运动缺陷的主要危险因素有关,这些危险因素的原因既有已知的也有未知的。越来越多的证据揭示了几种其他脂质的作用及其与α-syn 聚集的关联,α-syn 聚集物激活先天和适应性免疫系统并引发 PD 中的脑炎症。在这里,我们回顾了一些脂质的新兴作用,即甘油三酯(TG)、二甘油酯(DG)、甘油磷酸乙醇胺(GPE)、多不饱和脂肪酸(PUFA)、鞘脂、神经节苷脂、甘油磷脂(GPL)和胆固醇,以及它们与α-syn 聚集的关系以及先天和适应性免疫反应的诱导,这些反应会引发 PD 中的神经炎症。