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Title: | Perilipin-2 limits remyelination by preventing lipid droplet degradation | Authors: | LOIX, Melanie WOUTERS, Elien VANHERLE, Sam Dehairs, Jonas McManaman, James L. KEMPS, Hannelore SWINNEN , Jo HAIDAR, Mansour BOGIE, Jeroen HENDRIKS, Jerome |
Issue Date: | 2022 | Publisher: | SPRINGER BASEL AG | Source: | Cellular and molecular life sciences (Print), 79 (10) (Art N° 515) | Abstract: | Foamy macrophages and microglia containing lipid droplets (LDs) are a pathological hallmark of demyelinating disorders affecting the central nervous system (CNS). We and others showed that excessive accumulation of intracellular lipids drives these phagocytes towards a more inflammatory phenotype, thereby limiting CNS repair. To date, however, the mechanisms underlying LD biogenesis and breakdown in lipid-engorged phagocytes in the CNS, as well as their impact on foamy phagocyte biology and lesion progression, remain poorly understood. Here, we provide evidence that LD-associated protein perilipin-2 (PLIN2) controls LD metabolism in myelin-containing phagocytes. We show that PLIN2 protects LDs from lipolysis-mediated degradation, thereby impairing intracellular processing of myelin-derived lipids in phagocytes. Accordingly, loss of Plin2 stimulates LD turnover in foamy phagocytes, driving them towards a less inflammatory phenotype. Importantly, Plin2-deficiency markedly improves remyelination in the ex vivo brain slice model and in the in vivo cuprizone-induced demyelination model. In summary, we identify PLIN2 as a novel therapeutic target to prevent the pathogenic accumulation of LDs in foamy phagocytes and to stimulate remyelination. | Notes: | Hendriks, JJA (corresponding author), Hasselt Univ, Biomed Res Inst, Dept Immunol & Infect, Diepenbeek, Belgium.; Hendriks, JJA (corresponding author), Univ MS Ctr Hasselt, Pelt, Belgium. jerome.hendriks@uhasselt.be |
Keywords: | Lipid droplet associated protein;Foamy macrophages;Lipolysis;Lipophagy;Inflammation | Document URI: | http://hdl.handle.net/1942/38677 | ISSN: | 1420-682X | e-ISSN: | 1420-9071 | DOI: | 10.1007/s00018-022-04547-0 | ISI #: | 000853348700002 | Rights: | The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022 | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2023 |
Appears in Collections: | Research publications |
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