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Title: | The ApoA-I mimetic peptide 5A enhances remyelination by promoting clearance and degradation of myelin debris | Authors: | VANHERLE, Sam JORISSEN, Winde DIERCKX, Tess LOIX, Melanie GRAJCHEN, Elien MINGNEAU, Fleur GUNS, Jeroen GERVOIS, Pascal LAMBRICHTS, Ivo Dehairs, Jonas Swinnen, Johannes, V Mulder, Monique T. Remaley, Alan T. HAIDAR, Mansour HENDRIKS, Jerome BOGIE, Jeroen |
Issue Date: | 2022 | Publisher: | CELL PRESS | Source: | Cell Reports, 41 (6) (Art N° 111591) | Abstract: | The progressive nature of demyelinating diseases lies in the inability of the central nervous system (CNS) to induce proper remyelination. Recently, we and others demonstrated that a dysregulated innate immune response partially underlies failure of CNS remyelination. Extensive accumulation of myelin-derived lipids and an inability to process these lipids was found to induce a disease-promoting phagocyte phenotype. Hence, restoring the ability of these phagocytes to metabolize and efflux myelin-derived lipids represents a promising strategy to promote remyelination. Here, we show that ApoA-I mimetic peptide 5A, a molecule well known to promote activity of the lipid efflux transporter ABCA1, markedly enhances remyelination. Mechanistically, we find that the repair-inducing properties of 5A are attributable to increased clearance and metabolism of remyelination-inhibiting myelin debris via the fatty acid translocase protein CD36, which is transcriptionally controlled by the ABCA1-JAK2-STAT3 signaling pathway. Altogether, our findings indi-cate that 5A promotes remyelination by stimulating clearance and degradation of myelin debris. | Notes: | Bogie, JJF (corresponding author), Hasselt Univ, Biomed Res Inst, Dept Immunol & Infect, B-3590 Diepenbeek, Belgium.; Bogie, JJF (corresponding author), Univ MS Ctr Hasselt, B-3900 Pelt, Belgium. jeroen.bogie@uhasselt.be |
Keywords: | ApoA-I mimetic peptide 5A;CP: Neuroscience;lipid droplet degradation;myelin debris clearance;phagocyte;remyelination;Humans;Myelin Sheath;Apolipoprotein A-I;Peptides;Remyelination;Demyelinating Diseases | Document URI: | http://hdl.handle.net/1942/39129 | ISSN: | 2211-1247 | e-ISSN: | 2211-1247 | DOI: | 10.1016/j.celrep.2022.111591 | ISI #: | 000891242800004 | Rights: | 2022 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2023 |
Appears in Collections: | Research publications |
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The ApoA-I mimetic peptide 5A enhances remyelination by promoting clearance and degradation of myelin debris.pdf | Published version | 7.56 MB | Adobe PDF | View/Open |
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