TAILIEUCHUNG - Báo cáo khoa học: acids in the brain: D-serine in neurotransmission and neurodegeneration

The mammalian brain contains unusually high levels ofd-serine, ad-amino acid previously thought to be restricted to some bacteria and insects. In the last few years, studies from several groups have demonstrated that d-serine is a physiological co-agonist of the N-methyl d-aspartate (NMDA) type of glutamate receptor – a key excitatory neurotransmitter receptor in the brain. | MINIREVIEW D-Amino acids in the brain D-serine in neurotransmission and neurodegeneration Herman Wolosker Elena Dumin Livia Balan and Veronika N. Foltyn Department of Biochemistry B. Rappaport Faculty of Medicine Technion-Israellnstitute of Technology Haifa Israel Keywords D-serine gliotransmitter glutamate glycine L-serine neurodegeneration neurotransmission neurotoxicity NMDA receptor schizophrenia serine racemase Correspondence H. Wolosker Department of Biochemistry B. Rappaport Faculty of Medicine Technion-IsraelInstitute of Technology Haifa 31096 Israel Fax 972 4 8295384 Tel 972 4 8295386 E-mail hwolosker@ Received 30 January 2008 revised 14 April 2008 accepted 22 May 2008 doi The mammalian brain contains unusually high levels of D-serine a D-amino acid previously thought to be restricted to some bacteria and insects. In the last few years studies from several groups have demonstrated that D-serine is a physiological co-agonist of the N-methyl D-aspartate NMDA type of glutamate receptor - a key excitatory neurotransmitter receptor in the brain. D-Serine binds with high affinity to a co-agonist site at the NMDA receptors and along with glutamate mediates several important physiological and pathological processes including NMDA receptor transmission synaptic plasticity and neurotoxicity. In recent years biosynthetic degrada-tive and release pathways for D-serine have been identified indicating that D-serine may function as a transmitter. At first D-serine was described in astrocytes a class of glial cells that ensheathes neurons and release several transmitters that modulate neurotransmission. This led to the notion that D-serine is a glia-derived transmitter or gliotransmitter . However recent data indicate that serine racemase the D-serine biosynthetic enzyme is widely expressed in neurons of the brain suggesting that D-serine also has a neuronal origin. We now review these findings focusing on recent questions

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