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Multiple pathways of lipid dysregulation in amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis is a rapidly progressing neurodegenerative disease characterized by the degeneration of motor neurons and loss of various muscular functions. Dyslipidaemia is prevalent in amyotrophic lateral sclerosis with aberrant changes mainly in cholesterol ester and triglyceride....
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9825811/ https://www.ncbi.nlm.nih.gov/pubmed/36632187 http://dx.doi.org/10.1093/braincomms/fcac340 |
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author | Phan, Katherine He, Ying Bhatia, Surabhi Pickford, Russell McDonald, Gordon Mazumder, Srestha Timmins, Hannah C Hodges, John R Piguet, Olivier Dzamko, Nicolas Halliday, Glenda M Kiernan, Matthew C Kim, Woojin Scott |
author_facet | Phan, Katherine He, Ying Bhatia, Surabhi Pickford, Russell McDonald, Gordon Mazumder, Srestha Timmins, Hannah C Hodges, John R Piguet, Olivier Dzamko, Nicolas Halliday, Glenda M Kiernan, Matthew C Kim, Woojin Scott |
author_sort | Phan, Katherine |
collection | PubMed |
description | Amyotrophic lateral sclerosis is a rapidly progressing neurodegenerative disease characterized by the degeneration of motor neurons and loss of various muscular functions. Dyslipidaemia is prevalent in amyotrophic lateral sclerosis with aberrant changes mainly in cholesterol ester and triglyceride. Despite this, little is known about global lipid changes in amyotrophic lateral sclerosis or in relation to disease progression. The present study incorporated a longitudinal lipidomic analysis of amyotrophic lateral sclerosis serum with a comparison with healthy controls using advanced liquid chromatography-mass spectrometry. The results established that diglyceride, the precursor of triglyceride, was enriched the most, while ceramide was depleted the most in amyotrophic lateral sclerosis compared with controls, with the diglyceride species (18:1/18:1) correlating significantly to neurofilament light levels. The prenol lipid CoQ(8) was also decreased in amyotrophic lateral sclerosis and correlated to neurofilament light levels. Most interestingly, the phospholipid phosphatidylethanolamine and its three derivatives decreased with disease progression, in contrast to changes with normal ageing. Unsaturated lipids that are prone to lipid peroxidation were elevated with disease progression with increases in the formation of toxic lipid products. Furthermore, in vitro studies revealed that phosphatidylethanolamine synthesis modulated TARDBP expression in SH-SY5Y neuronal cells. Finally, diglyceride, cholesterol ester and ceramide were identified as potential lipid biomarkers for amyotrophic lateral sclerosis diagnosis and monitoring disease progression. In summary, this study represents a longitudinal lipidomics analysis of amyotrophic lateral sclerosis serum and has provided new insights into multiple pathways of lipid dysregulation in amyotrophic lateral sclerosis. |
format | Online Article Text |
id | pubmed-9825811 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-98258112023-01-10 Multiple pathways of lipid dysregulation in amyotrophic lateral sclerosis Phan, Katherine He, Ying Bhatia, Surabhi Pickford, Russell McDonald, Gordon Mazumder, Srestha Timmins, Hannah C Hodges, John R Piguet, Olivier Dzamko, Nicolas Halliday, Glenda M Kiernan, Matthew C Kim, Woojin Scott Brain Commun Original Article Amyotrophic lateral sclerosis is a rapidly progressing neurodegenerative disease characterized by the degeneration of motor neurons and loss of various muscular functions. Dyslipidaemia is prevalent in amyotrophic lateral sclerosis with aberrant changes mainly in cholesterol ester and triglyceride. Despite this, little is known about global lipid changes in amyotrophic lateral sclerosis or in relation to disease progression. The present study incorporated a longitudinal lipidomic analysis of amyotrophic lateral sclerosis serum with a comparison with healthy controls using advanced liquid chromatography-mass spectrometry. The results established that diglyceride, the precursor of triglyceride, was enriched the most, while ceramide was depleted the most in amyotrophic lateral sclerosis compared with controls, with the diglyceride species (18:1/18:1) correlating significantly to neurofilament light levels. The prenol lipid CoQ(8) was also decreased in amyotrophic lateral sclerosis and correlated to neurofilament light levels. Most interestingly, the phospholipid phosphatidylethanolamine and its three derivatives decreased with disease progression, in contrast to changes with normal ageing. Unsaturated lipids that are prone to lipid peroxidation were elevated with disease progression with increases in the formation of toxic lipid products. Furthermore, in vitro studies revealed that phosphatidylethanolamine synthesis modulated TARDBP expression in SH-SY5Y neuronal cells. Finally, diglyceride, cholesterol ester and ceramide were identified as potential lipid biomarkers for amyotrophic lateral sclerosis diagnosis and monitoring disease progression. In summary, this study represents a longitudinal lipidomics analysis of amyotrophic lateral sclerosis serum and has provided new insights into multiple pathways of lipid dysregulation in amyotrophic lateral sclerosis. Oxford University Press 2022-12-26 /pmc/articles/PMC9825811/ /pubmed/36632187 http://dx.doi.org/10.1093/braincomms/fcac340 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Phan, Katherine He, Ying Bhatia, Surabhi Pickford, Russell McDonald, Gordon Mazumder, Srestha Timmins, Hannah C Hodges, John R Piguet, Olivier Dzamko, Nicolas Halliday, Glenda M Kiernan, Matthew C Kim, Woojin Scott Multiple pathways of lipid dysregulation in amyotrophic lateral sclerosis |
title | Multiple pathways of lipid dysregulation in amyotrophic lateral sclerosis |
title_full | Multiple pathways of lipid dysregulation in amyotrophic lateral sclerosis |
title_fullStr | Multiple pathways of lipid dysregulation in amyotrophic lateral sclerosis |
title_full_unstemmed | Multiple pathways of lipid dysregulation in amyotrophic lateral sclerosis |
title_short | Multiple pathways of lipid dysregulation in amyotrophic lateral sclerosis |
title_sort | multiple pathways of lipid dysregulation in amyotrophic lateral sclerosis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9825811/ https://www.ncbi.nlm.nih.gov/pubmed/36632187 http://dx.doi.org/10.1093/braincomms/fcac340 |
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