Please use this identifier to cite or link to this item:
http://hdl.handle.net/1942/36986
Title: | Targeting lipophagy in macrophages improves repair in multiple sclerosis | Authors: | HAIDAR, Mansour LOIX, Melanie VANHERLE, Sam DIERCKX, Tess VANGANSEWINKEL, Tim GERVOIS, Pascal WOLFS, Esther LAMBRICHTS, Ivo BOGIE, Jeroen HENDRIKS, Jerome |
Issue Date: | 2022 | Publisher: | Source: | Autophagy, | Status: | Early view | Abstract: | Foamy macrophages containing abundant intracellular myelin remnants are an important pathological hallmark of multiple sclerosis. Reducing the intracellular lipid burden in foamy macrophages is considered a promising therapeutic strategy to induce a phagocyte phenotype that promotes central nervous system repair. Recent research from our group showed that sustained intracellular accumulation of myelin-derived lipids skews these phagocytes toward a disease-promoting and more inflammatory phenotype. Our data now demonstrate that disturbed lipophagy, a selective form of autophagy that helps with the degradation of lipid droplets, contributes to the induction of this phenotype. Stimulating autophagy using the natural disaccharide trehalose reduced the lipid load and inflammatory phenotype of myelin-laden macrophages. Importantly, trehalose was able to boost remyelination in the ex vivo brain slice model and the in vivo cuprizone-induced demyelination model. In summary, our results provide a molecular rationale for impaired metabolism of myelin-derived lipids in macrophages, and identify lipophagy induction as a promising treatment strategy to promote remyelination. | Keywords: | Lipid droplets;lipophagy;multiple sclerosis;phagocyte;remyelination | Document URI: | http://hdl.handle.net/1942/36986 | ISSN: | 1554-8627 | e-ISSN: | 1554-8635 | DOI: | 10.1080/15548627.2022.2047343 | ISI #: | 000768717200001 | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2023 |
Appears in Collections: | Research publications |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Targeting lipophagy in macrophages improves repair in multiple sclerosis.pdf Restricted Access | Published version | 4.53 MB | Adobe PDF | View/Open Request a copy |
Haidar, Loix, et al., 2021. Revised manuscript_Final R3.pdf | Peer-reviewed author version | 2.67 MB | Adobe PDF | View/Open |
WEB OF SCIENCETM
Citations
12
checked on Apr 15, 2024
Page view(s)
86
checked on Aug 31, 2022
Download(s)
6
checked on Aug 31, 2022
Google ScholarTM
Check
Altmetric
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.