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Research has indicated that the -KG-consuming protein Tet3 (the primary -KG-dependent dioxygenase in neurons that converts 5-methyl-dC into 5-hydroxymethyl-dC and then into 5-formyl- and 5-carboxy-dC) reroutes mitochondrial GDH, which converts glutamate into -KG in an NAD + -dependent manner, to the nucleus, indicating the onsite production of -KG

The influence of HO-1 on the TME immunoprofile was highlighted by Alaluf et al., who reported that myeloid-specific ablation of HO-1 induced global transcriptional and epigenetic alterations not limited to the conventional M1/M2 polarization state of TAMs, but rather leading to extensive dysregulation of the central molecular signature of the TME (45)

10.3389/fphar.2025.1540559 38 GorugantulaL

To date, the effects of NF-B on oligodendrocytes in normal myelin formation and MS remain ambiguous, and as oligodendrocytes are the main target of MS, further efforts are required to provide clues for future therapeutic approaches