N-acetyl-aspartate metabolism at the interface of cancer, immunity, and neurodegeneration

N-acetyl-L-aspartic acid (NAA) is a prominent amino acid derivative primarily associated with vertebrate brain metabolism. This review delineates the critical role of NAA across various cell types and its significance in pathophysiological contexts, including Canavan disease and cancer metabolism. Although traditionally linked with myelination and aspartoacylase-driven carbon donation, its significance as a carbon source for myelination remains debated. Evidence suggests that intact NAA might substantially impact cellular signaling, particularly processes such as histone acetylation. Beyond the brain, NAA metabolism's relevance is evident in diverse tissues, such as adipocytes, immune cells, and notably, cancer cells. In several cancer types, there is an observed upregulation of NAA synthesis accompanied by a simultaneous downregulation of its degradation. This pattern highlights the potential signaling role of intact NAA in disease.