2. Academic Validation
  3. The ApoA-I mimetic peptide 5A enhances remyelination by promoting clearance and degradation of myelin debris

The ApoA-I mimetic peptide 5A enhances remyelination by promoting clearance and degradation of myelin debris

  • Cell Rep. 2022 Nov 8;41(6):111591. doi: 10.1016/j.celrep.2022.111591.
Sam Vanherle 1,  Winde Jorissen 1,  Tess Dierckx 1,  Melanie Loix 1,  Elien Grajchen 1,  Fleur Mingneau 1,  Jeroen Guns 1,  Pascal Gervois 2,  Ivo Lambrichts 2,  Jonas Dehairs 3,  Johannes V Swinnen 3,  Monique T Mulder 4,  Alan T Remaley 5,  Mansour Haidar 1,  Jerome J A Hendriks 1,  Jeroen J F Bogie 6
Affiliations

Affiliations

  • 1 Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, 3590 Diepenbeek, Belgium; University MS Center Hasselt, 3900 Pelt, Belgium.
  • 2 Department of Cardio and Organs Systems, Biomedical Research Institute, Hasselt University, 3590 Diepenbeek, Belgium.
  • 3 Department of Oncology, Laboratory of Lipid Metabolism and Cancer, Leuven Cancer Institute, University of Leuven, 3000 Leuven, Belgium.
  • 4 Department of Internal Medicine, Erasmus University Medical Center, 3015 Rotterdam, the Netherlands.
  • 5 Lipoprotein Metabolism Laboratory, Translational Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • 6 Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, 3590 Diepenbeek, Belgium; University MS Center Hasselt, 3900 Pelt, Belgium. Electronic address: [email protected].
PMID: 36351388 DOI: 10.1016/j.celrep.2022.111591
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 indicate that 5A promotes remyelination by stimulating clearance and degradation of myelin debris.

Keywords

ApoA-I mimetic peptide 5A; CP: Neuroscience; lipid droplet degradation; myelin debris clearance; phagocyte; remyelination.

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