Increased VLCFA-lipids and ELOVL4 underlie neurodegeneration in frontotemporal dementia

Abstract Rare, yet biologically critical, lipids that contain very long chain fatty acids (VLCFA-lipids) are synthesized in the brain by the enzyme ELOVL4. High levels of VLCFA-lipids are toxic to cells and excess VLCFA-lipids are actively removed by ABCD1 in an ATP-dependent manner. Virtually nothi...

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Autores principales:	Ying He, Katherine Phan, Surabhi Bhatia, Russell Pickford, YuHong Fu, Yue Yang, John R. Hodges, Olivier Piguet, Glenda M. Halliday, Woojin Scott Kim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a3ec9702bb7d490a87d9e995c901b490
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spelling	oai:doaj.org-article:a3ec9702bb7d490a87d9e995c901b4902021-11-08T10:46:18ZIncreased VLCFA-lipids and ELOVL4 underlie neurodegeneration in frontotemporal dementia10.1038/s41598-021-00870-x2045-2322https://doaj.org/article/a3ec9702bb7d490a87d9e995c901b4902021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-00870-xhttps://doaj.org/toc/2045-2322Abstract Rare, yet biologically critical, lipids that contain very long chain fatty acids (VLCFA-lipids) are synthesized in the brain by the enzyme ELOVL4. High levels of VLCFA-lipids are toxic to cells and excess VLCFA-lipids are actively removed by ABCD1 in an ATP-dependent manner. Virtually nothing is known about the impact of VLCFA-lipids in neurodegenerative diseases. Here, we investigated the possible role of VLCFA-lipids in frontotemporal dementia (FTD), which is a leading cause of younger-onset dementia. Using quantitative discovery lipidomics, we identified three VLCFA-lipid species that were significantly increased in FTD brain compared to controls, with strong correlations with ELOVL4. Increases in ELOVL4 expression correlated with significant decreases in the membrane-bound synaptophysin in FTD brain. Furthermore, increases in ABCD1 expression correlated with increases in VLCFA-lipids. We uncovered a new pathomechanism that is pertinent to understanding the pathogenesis of FTD.Ying HeKatherine PhanSurabhi BhatiaRussell PickfordYuHong FuYue YangJohn R. HodgesOlivier PiguetGlenda M. HallidayWoojin Scott KimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ying He Katherine Phan Surabhi Bhatia Russell Pickford YuHong Fu Yue Yang John R. Hodges Olivier Piguet Glenda M. Halliday Woojin Scott Kim Increased VLCFA-lipids and ELOVL4 underlie neurodegeneration in frontotemporal dementia
description	Abstract Rare, yet biologically critical, lipids that contain very long chain fatty acids (VLCFA-lipids) are synthesized in the brain by the enzyme ELOVL4. High levels of VLCFA-lipids are toxic to cells and excess VLCFA-lipids are actively removed by ABCD1 in an ATP-dependent manner. Virtually nothing is known about the impact of VLCFA-lipids in neurodegenerative diseases. Here, we investigated the possible role of VLCFA-lipids in frontotemporal dementia (FTD), which is a leading cause of younger-onset dementia. Using quantitative discovery lipidomics, we identified three VLCFA-lipid species that were significantly increased in FTD brain compared to controls, with strong correlations with ELOVL4. Increases in ELOVL4 expression correlated with significant decreases in the membrane-bound synaptophysin in FTD brain. Furthermore, increases in ABCD1 expression correlated with increases in VLCFA-lipids. We uncovered a new pathomechanism that is pertinent to understanding the pathogenesis of FTD.
format	article
author	Ying He Katherine Phan Surabhi Bhatia Russell Pickford YuHong Fu Yue Yang John R. Hodges Olivier Piguet Glenda M. Halliday Woojin Scott Kim
author_facet	Ying He Katherine Phan Surabhi Bhatia Russell Pickford YuHong Fu Yue Yang John R. Hodges Olivier Piguet Glenda M. Halliday Woojin Scott Kim
author_sort	Ying He
title	Increased VLCFA-lipids and ELOVL4 underlie neurodegeneration in frontotemporal dementia
title_short	Increased VLCFA-lipids and ELOVL4 underlie neurodegeneration in frontotemporal dementia
title_full	Increased VLCFA-lipids and ELOVL4 underlie neurodegeneration in frontotemporal dementia
title_fullStr	Increased VLCFA-lipids and ELOVL4 underlie neurodegeneration in frontotemporal dementia
title_full_unstemmed	Increased VLCFA-lipids and ELOVL4 underlie neurodegeneration in frontotemporal dementia
title_sort	increased vlcfa-lipids and elovl4 underlie neurodegeneration in frontotemporal dementia
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a3ec9702bb7d490a87d9e995c901b490
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Increased VLCFA-lipids and ELOVL4 underlie neurodegeneration in frontotemporal dementia

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