| Autor: |
Sam Vanherle, Jeroen Guns, Melanie Loix, Fleur Mingneau, Tess Dierckx, Tim Vangansewinkel, Esther Wolfs, Paula Pincela Lins, Annelies Bronckaers, Ivo Lambrichts, Jonas Dehairs, Johannes V. Swinnen, Sanne G.S. Verberk, Mansour Haidar, Jerome J.A. Hendriks, Jeroen F.J. Bogie |
| Rok vydání: |
2022 |
| Popis: |
Macrophages play major roles in the pathophysiology of various neurological disorders, being involved in seemingly opposing processes such as lesion progression and resolution. Yet, the molecular mechanisms that drive their harmful and benign effector functions remain poorly understood. Here, we demonstrate that extracellular vesicles (EVs) secreted by repair-associated macrophages (RAMs) enhance remyelinationex vivoandin vivoby promoting the differentiation of oligodendrocyte precursor cells (OPCs). Guided by lipidomic analysis and applying cholesterol depletion and enrichment strategies, we find that EVs released by RAMs show markedly elevated cholesterol levels and that cholestserol abundance controls their reparative impact on OPC maturation and remyelination. Mechanistically, EV-associated cholesterol was found to promote OPC differentiation through direct membrane fusion. Collectively, our findings highlight that EVs are essential for cholesterol trafficking in the brain and that changes in cholesterol abundance dictate the reparative impact of EVs released by macrophages in the brain, potentially having broad implications for therapeutic strategies aimed at promoting repair in neurodegenerative disorders. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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