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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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-00870-x |
| _version_ | 1831563909416353792 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-17T11:04:05Z |
| format | Article |
| id | doaj.art-a3ec9702bb7d490a87d9e995c901b490 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-17T11:04:05Z |
| publishDate | 2021-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-a3ec9702bb7d490a87d9e995c901b4902022-12-21T21:51:38ZengNature PortfolioScientific Reports2045-23222021-11-0111111110.1038/s41598-021-00870-xIncreased VLCFA-lipids and ELOVL4 underlie neurodegeneration in frontotemporal dementiaYing He0Katherine Phan1Surabhi Bhatia2Russell Pickford3YuHong Fu4Yue Yang5John R. Hodges6Olivier Piguet7Glenda M. Halliday8Woojin Scott Kim9Brain and Mind Centre and School of Medical Sciences, The University of SydneyBrain and Mind Centre and School of Medical Sciences, The University of SydneyBrain and Mind Centre and School of Medical Sciences, The University of SydneyBioanalytical Mass Spectrometry Facility, University of New South WalesBrain and Mind Centre and School of Medical Sciences, The University of SydneyBrain and Mind Centre and School of Medical Sciences, The University of SydneyBrain and Mind Centre and School of Medical Sciences, The University of SydneyBrain and Mind Centre and School of Psychology, The University of SydneyBrain and Mind Centre and School of Medical Sciences, The University of SydneyBrain and Mind Centre and School of Medical Sciences, The University of SydneyAbstract 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.https://doi.org/10.1038/s41598-021-00870-x |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | Increased VLCFA-lipids and ELOVL4 underlie neurodegeneration in frontotemporal dementia |
| title_sort | increased vlcfa lipids and elovl4 underlie neurodegeneration in frontotemporal dementia |
| url | https://doi.org/10.1038/s41598-021-00870-x |
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