L-2-hydroxyglutarate impairs neuronal differentiation through epigenetic activation of MYC expression - PubMed
6 hours ago
- #Neurodevelopment
- #Metabolism
- #Epigenetics
- L-2-hydroxyglutarate (L-2HG) impairs neuronal differentiation by epigenetically activating MYC expression.
- L2HGDH deficiency leads to L-2HG accumulation, causing neural progenitor cell hyperproliferation and defective neuronal differentiation.
- Inhibition of glutaminase reduces L-2HG levels and promotes neuronal differentiation.
- L-2HG inhibits KDM5 histone demethylases, leading to increased H3K4me2/3 markers and elevated MYC expression.
- Normalizing MYC expression, either genetically or pharmacologically, restores neuronal differentiation despite altered histone methylation.