Glycosphingolipid metabolism and its role in ageing and Parkinson's disease.
Glycosphingolipid metabolism and its role in ageing and Parkinson's disease.
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DOI：
10.1007/s10719-021-10023-x
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发表时间：
2022-03
影响因子：
3
通讯作者：
Platt FM
中科院分区：
文献类型：
--
作者：
Wallom KL;Fernández-Suárez ME;Priestman DA;Te Vruchte D;Huebecker M;Hallett PJ;Isacson O;Platt FM
溶酶体糖脑苷酶基因（GBA）变异是帕金森病（PD）的危险因素，越来越多的证据表明其功能丧失机制。这种遗传关联提出的一个问题是，参与鞘脂代谢其他方面的基因变异是否也与帕金森病有关。最近对散发性帕金森病的研究发现，与鞘糖脂代谢疾病相关的多个基因变异与帕金森病有关。GSL生物合成是一个复杂的途径，涉及多种酶在高尔基体的协调作用。GSL分解代谢发生在溶酶体中，依赖于特定底物和聚糖键的多种酸水解酶的作用。多种GSL分解代谢基因的变异在PD中呈杂合状态，这一发现突出了GSL在健康大脑中的重要性，以及脂质失衡和溶酶体功能障碍如何与正常衰老和神经退行性疾病相关。在本文中，我们将探讨溶酶体贮积症和帕金森病之间的联系，在正常衰老、溶酶体贮积症和帕金森病中所见的GSL变化，以及这些变化影响神经退行性变的机制。
It is well established that lysosomal glucocerebrosidase gene (GBA) variants are a risk factor for Parkinson’s disease (PD), with increasing evidence suggesting a loss of function mechanism. One question raised by this genetic association is whether variants of genes involved in other aspects of sphingolipid metabolism are also associated with PD. Recent studies in sporadic PD have identified variants in multiple genes linked to diseases of glycosphingolipid (GSL) metabolism to be associated with PD. GSL biosynthesis is a complex pathway involving the coordinated action of multiple enzymes in the Golgi apparatus. GSL catabolism takes place in the lysosome and is dependent on the action of multiple acid hydrolases specific for certain substrates and glycan linkages. The finding that variants in multiple GSL catabolic genes are over-represented in PD in a heterozygous state highlights the importance of GSLs in the healthy brain and how lipid imbalances and lysosomal dysfunction are associated with normal ageing and neurodegenerative diseases. In this article we will explore the link between lysosomal storage disorders and PD, the GSL changes seen in both normal ageing, lysosomal storage disorders (LSDs) and PD and the mechanisms by which these changes can affect neurodegeneration.
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影响因子：
3.6
作者：
Cullen, Valerie;Lindfors, Maria;Ng, Juliana;Paetau, Anders;Swinton, Erika;Kolodziej, Piotr;Boston, Heather;Saftig, Paul;Woulfe, John;Feany, Mel B.;Myllykangas, Liisa;Schlossmacher, Michael G.;Tyynela, Jaana
通讯作者：
Tyynela, Jaana
影响因子：
64.8
作者：
Cruts, Marc;Gijselinck, Ilse;Van Broeckhoven, Christine
通讯作者：
Van Broeckhoven, Christine
影响因子：
3.5
作者：
Cachon-Gonzalez, Maria-Begona;Wang, Susan Z.;Cox, Timothy M.
通讯作者：
Cox, Timothy M.
影响因子：
14.5
作者：
Blauwendraat, Cornelis;Reed, Xylena;Singleton, Andrew B.
通讯作者：
Singleton, Andrew B.
影响因子：
9.9
作者：
Anheim, M.;Elbaz, A.;Brice, A.
通讯作者：
Brice, A.