Deficiency of galactosyl-ceramidase in adult oligodendrocytes worsens disease severity during chronic experimental allergic encephalomyelitis.

ABSTRACT: Galactosyl-ceramidase (GALC) is a ubiquitous lysosomal enzyme crucial for the correct myelination of the mammalian nervous system during early postnatal development. However, the physiological consequence of GALC deficiency in the adult brain remains unknown. In this study, we found that mice with conditional ablation of GALC activity in post-myelinating oligodendrocytes were lethally sensitized when challenged with chronic experimental allergic encephalomyelitis (EAE), in contrast with the non-lethal dysmyelination observed in Galc-ablated mice without the EAE challenge. Mechanistically, we found strong inflammatory demyelination without remyelination and an impaired fusion of lysosomes and autophagosomes with accumulation of myelin debris after a transcription factor EB-dependent increas

SUBMITTER: Saldivia N 

PROVIDER: S-EPMC11403238 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature