Myeloid cell-associated aromatic amino acid metabolism facilitates CNS myelin regeneration

The enzyme interleukin-4 induced 1 (IL4I1) is expressed in myeloid cells during remyelination in mouse models of multiple sclerosis (MS). Knocking out IL4I1 in myeloid cells leads to impaired remyelination efficiency. IL4I1 converts aromatic amino acids into alpha-keto acids (AKAs) like phenylpyruvic acid (PPA), indole-3-pyruvic acid (IPA), and 4-hydroxyphenylpyruvic acid (HPPA). The levels of these AKAs are reduced in MS lesions when IL4I1 is knocked out. People with progressive MS also show reduced levels of PPA and HPPA compared to those with relapsing-remitting MS and healthy controls. Higher PPA levels correlate with better MRI measures in people with MS. Treating inflammatory myeloid cells with AKAs reduces inflammatory cytokine production. AKAs also promote oligodendrocyte maturation indirectly by modulating microglia inflammation. <a href="https://medium.com/@axialxyz/myeloid-cell-associated-aromatic-amino-acid-metabolism-facilitates-cns-myelin-regeneration-b5b91d3c914e">Visit Now</a>