Glycosphingolipids and neuroinflammation in Parkinson's disease.
Glycosphingolipids and neuroinflammation in Parkinson's disease.
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DOI：
10.1186/s13024-020-00408-1
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发表时间：
2020-10-17
影响因子：
15.1
通讯作者：
Chartier-Harlin MC
中科院分区：
文献类型：
--
作者：
Belarbi K;Cuvelier E;Bonte MA;Desplanque M;Gressier B;Devos D;Chartier-Harlin MC
帕金森病是一种进行性神经退行性疾病，其特征在于黑质纹状体通路的多巴胺能神经元的损失和称为路易体的神经元内含物的形成。慢性神经炎症是该疾病的另一个标志，被认为在神经退行性过程中起重要作用。鞘糖脂是一种定义明确的脂质亚类，调节大脑功能的关键方面，最近成为炎症过程的有效调节剂。在帕金森氏病中已经报道了鞘糖脂代谢的失调。然而，鞘糖脂和帕金森病神经炎症之间的相互关系并不清楚。这篇综述提供了一个全面的概述鞘糖脂代谢和免疫介导的机制参与帕金森病神经炎症之间的联系。在简要介绍了鞘糖脂在大脑中的代谢和功能后，总结了支持鞘糖脂（即葡萄糖神经酰胺或特定神经节苷脂）在帕金森病中失调的证据。然后，根据人类遗传性溶酶体鞘糖脂贮积症和基因工程动物研究的数据，概述了这些失调对神经炎症的影响。最后，鞘糖脂可以控制帕金森病神经炎症的关键分子机制被强调。这些包括炎性小体激活和促炎细胞因子的分泌、钙稳态改变、血脑屏障通透性的变化、外周免疫细胞的募集或自身抗体的产生。
Parkinson's disease is a progressive neurodegenerative disease characterized by the loss of dopaminergic neurons of the nigrostriatal pathway and the formation of neuronal inclusions known as Lewy bodies. Chronic neuroinflammation, another hallmark of the disease, is thought to play an important role in the neurodegenerative process. Glycosphingolipids are a well-defined subclass of lipids that regulate crucial aspects of the brain function and recently emerged as potent regulators of the inflammatory process. Deregulation in glycosphingolipid metabolism has been reported in Parkinson’s disease. However, the interrelationship between glycosphingolipids and neuroinflammation in Parkinson’s disease is not well known. This review provides a thorough overview of the links between glycosphingolipid metabolism and immune-mediated mechanisms involved in neuroinflammation in Parkinson’s disease. After a brief presentation of the metabolism and function of glycosphingolipids in the brain, it summarizes the evidences supporting that glycosphingolipids (i.e. glucosylceramides or specific gangliosides) are deregulated in Parkinson’s disease. Then, the implications of these deregulations for neuroinflammation, based on data from human inherited lysosomal glycosphingolipid storage disorders and gene-engineered animal studies are outlined. Finally, the key molecular mechanisms by which glycosphingolipids could control neuroinflammation in Parkinson’s disease are highlighted. These include inflammasome activation and secretion of pro-inflammatory cytokines, altered calcium homeostasis, changes in the blood-brain barrier permeability, recruitment of peripheral immune cells or production of autoantibodies.
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影响因子：
3.5
作者：
Bras J;Guerreiro R;Darwent L;Parkkinen L;Ansorge O;Escott-Price V;Hernandez DG;Nalls MA;Clark LN;Honig LS;Marder K;Van Der Flier WM;Lemstra A;Scheltens P;Rogaeva E;St George-Hyslop P;Londos E;Zetterberg H;Ortega-Cubero S;Pastor P;Ferman TJ;Graff-Radford NR;Ross OA;Barber I;Braae A;Brown K;Morgan K;Maetzler W;Berg D;Troakes C;Al-Sarraj S;Lashley T;Compta Y;Revesz T;Lees A;Cairns N;Halliday GM;Mann D;Pickering-Brown S;Dickson DW;Singleton A;Hardy J
通讯作者：
Hardy J
影响因子：
7.8
作者：
Aflaki E;Moaven N;Borger DK;Lopez G;Westbroek W;Chae JJ;Marugan J;Patnaik S;Maniwang E;Gonzalez AN;Sidransky E
通讯作者：
Sidransky E
影响因子：
11.2
作者：
ARGOV, Z;NAVON, R
通讯作者：
NAVON, R
影响因子：
15.9
作者：
Brochard, Vanessa;Combadiere, Behazine;Hunot, Stephane
通讯作者：
Hunot, Stephane
不变的天然杀手T细胞识别微生物危险信号引起的脂质自抗原。
影响因子：
30.5
作者：
Brennan, Patrick J.;Tatituri, Raju V. V.;Brigl, Manfred;Kim, Edy Y.;Tuli, Amit;Sanderson, Joseph P.;Gadola, Stephan D.;Hsu, Fong-Fu;Besra, Gurdyal S.;Brenner, Michael B.
通讯作者：
Brenner, Michael B.