Loss of oligodendrocyte transcription factor 2 protein expression in metabolically stressed oligodendrocytes - PubMed
8 hours ago
- #demyelination
- #multiple sclerosis
- #oligodendrocyte stress
- Oligodendrocyte dysfunction in demyelinating diseases like multiple sclerosis (MS) involves a stress-induced, post-transcriptional loss of OLIG2 protein expression.
- In the cuprizone model, stressed oligodendrocytes show early OLIG2low expression followed by OLIG2-negative states, particularly in cells with integrated stress response markers.
- OLIG2 protein loss occurs without reduced Olig2 mRNA levels, indicating it's a post-transcriptional event missed by RNA profiling.
- Similar OLIG2 loss is seen in metabolic stress models and post-mortem MS lesions, suggesting it's a reversible phenotype.
- Pharmacological intervention with siponimod in the cuprizone model attenuates OLIG2 loss, indicating modifiability.
- OLIG2 protein loss may serve as an early stress indicator and therapeutic target for preserving myelin integrity.