D-Serine in neurobiology: CNS neurotransmission and neuromodulation

Homochirality is fundamental for life. L-Amino acids are exclusively used as substrates for the polymerization and formation of peptides and proteins in living systems. However, D- amino acids were recently detected in various living organisms, including mammals. Of these D-amino acids, D-serine has been most extensively studied. D-Serine was found to play an important role as a neurotransmitter in the human central nervous system (CNS) by binding to the N-methyl- D-aspartate receptor (NMDAr). D-Serine binds with high affinity to a co-agonist site at the NMDAr and, along with glutamate, mediates several vital physiological and pathological processes, including NMDAr transmission, synaptic plasticity and neurotoxicity. Therefore, a key role for D-serine as a determinant of NMDAr mediated neurotransmission in mammalian CNS has been suggested. In this context, we review the known functions of D-serine in human physiology, such as CNS development, and pathology, such as neuro-psychiatric and neurodegenerative diseases related to NMDAr dysfunction.