Journal article
Glycosphingolipid metabolism and its role in ageing and Parkinson’s disease
- Abstract:
- 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
Actions
Access Document
- Files:
-
-
(Preview, Version of record, pdf, 1.7MB, Terms of use)
-
- Publisher copy:
- /10.1007/s10719-021-10023-x
Authors
- Publisher:
- Springer
- Journal:
- Glycoconjugate Journal More from this journal
- Volume:
- 39
- Pages:
- 39–53
- Publication date:
- 2021-11-10
- Acceptance date:
- 2021-09-24
- DOI:
- EISSN:
-
1573-4986
- ISSN:
-
0282-0080
- Language:
-
English
- Keywords:
- Pubs id:
-
1203304
- Local pid:
-
pubs:1203304
- Deposit date:
-
2021-10-18
- ARK identifier:
Terms of use
- Copyright holder:
- Wallom et al
- Copyright date:
- 2021
- Rights statement:
- © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
If you are the owner of this record, you can report an update to it here: Report update to this record