Bibliographic Details
| Title: |
Peroxisomal defects in microglial cells induce a disease-associated microglial signature |
| Authors: |
Quentin Raas, Ali Tawbeh, Mounia Tahri-Joutey, Catherine Gondcaille, Céline Keime, Romain Kaiser, Doriane Trompier, Boubker Nasser, Valerio Leoni, Emma Bellanger, Maud Boussand, Yannick Hamon, Alexandre Benani, Francesca Di Cara, Caroline Truntzer, Mustapha Cherkaoui-Malki, Pierre Andreoletti, Stéphane Savary |
| Source: |
Frontiers in Molecular Neuroscience, Vol 16 (2023) |
| Publisher Information: |
Frontiers Media S.A., 2023. |
| Publication Year: |
2023 |
| Collection: |
LCC:Neurosciences. Biological psychiatry. Neuropsychiatry |
| Subject Terms: |
peroxisome, adrenoleukodystrophy (X-ALD), microglia, lysosome, lipid metabolism, autophagy, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571 |
| More Details: |
Microglial cells ensure essential roles in brain homeostasis. In pathological condition, microglia adopt a common signature, called disease-associated microglial (DAM) signature, characterized by the loss of homeostatic genes and the induction of disease-associated genes. In X-linked adrenoleukodystrophy (X-ALD), the most common peroxisomal disease, microglial defect has been shown to precede myelin degradation and may actively contribute to the neurodegenerative process. We previously established BV-2 microglial cell models bearing mutations in peroxisomal genes that recapitulate some of the hallmarks of the peroxisomal β-oxidation defects such as very long-chain fatty acid (VLCFA) accumulation. In these cell lines, we used RNA-sequencing and identified large-scale reprogramming for genes involved in lipid metabolism, immune response, cell signaling, lysosome and autophagy, as well as a DAM-like signature. We highlighted cholesterol accumulation in plasma membranes and observed autophagy patterns in the cell mutants. We confirmed the upregulation or downregulation at the protein level for a few selected genes that mostly corroborated our observations and clearly demonstrated increased expression and secretion of DAM proteins in the BV-2 mutant cells. In conclusion, the peroxisomal defects in microglial cells not only impact on VLCFA metabolism but also force microglial cells to adopt a pathological phenotype likely representing a key contributor to the pathogenesis of peroxisomal disorders. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1662-5099 |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fnmol.2023.1170313/full; https://doaj.org/toc/1662-5099 |
| DOI: |
10.3389/fnmol.2023.1170313 |
| Access URL: |
https://doaj.org/article/e61fd3afe1cd4f0d9a7144d4fea8bc3c |
| Accession Number: |
edsdoj.61fd3afe1cd4f0d9a7144d4fea8bc3c |
| Database: |
Directory of Open Access Journals |
