Serine racemase: a key player in neuron activity and in neuropathologies

Serine racemase is the pyridoxal 5'-phosphate-dependent enzyme that catalyzes L-serine racemisation to D-serine, and L- and D-serine beta-elimination in mammalian brain. D-serine is the essential co-agonist of the N-methyl-D-aspartate receptor, that mediates neurotransmission, synaptic plasticity, cell migration and long term potentiation. High and low D-serine levels have been associated with distinct neuropathologies, aging-related deficits and psychiatric disorders due to either hyper- or hypo-activation of the receptor. Serine racemase dual activity is regulated by ATP, divalent cations, cysteine nitrosylation, post-translational modifications, and interactions with proteins that bind either at the N- or C-terminus. A detailed elucidation of the molecular basis of catalysis, regulation and conformational plasticity, as well as enzyme and D-serine localization and neurons and astrocytes cross-talk, opens the way to the development of enzyme inhibitors and effectors for tailored therapeutic treatments.