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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Neurobiology through the looking-glass: D-serine as a new glial-derived transmitter.
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Neurobiology through the looking-glass: D-serine as a new glial-derived transmitter.

机译：通过窥镜观察神经生物学：D-丝氨酸是一种新的神经胶质来源的递质。

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摘要

D-Amino acids have been known to be present in bacteria for more than 50 years, but only recently they were identified in mammals. The occurrence of D-amino acids in mammals challenge classic concepts in biology in which only L-amino acids would be present or thought to play important roles. Recent discoveries uncovered a role of endogenous D-serine as a putative glial-derived transmitter that regulates glutamatergic neurotransmission in mammalian brain. Free D-serine levels in the brain are about one third of L-serine values and its extracellular concentration is higher than many common L-amino acids. D-Serine occurs in protoplasmic astrocytes, a class of glial cells that ensheath the synapses and modulate neuronal activity. Biochemical and electrophysiological studies suggest that endogenous D-serine is a physiological modulator at the co-agonist site of NMDA-type of glutamate receptors. We previously showed that D-serine is synthesized by a glial serine racemase, a novel enzyme converting L- to D-serine in mammalian brain. The enzyme requires pyridoxal 5'-phosphate and it was the first racemase to be cloned from eucaryotes. Inhibitors of serine racemase have therapeutic implications for pathological processes in which over-stimulation of NMDA receptors takes place, such as stroke and neurodegenerative diseases. Here, we review the role of endogenous D-serine in modulating NMDA neurotransmission, its biosynthetic apparatus and the potential usefulness of serine racemase inhibitors as a novel neuroprotective strategy to decrease glutamate/NMDA excitotoxicity.
机译：已知D-氨基酸存在于细菌中已有50多年的历史，但直到最近才在哺乳动物中被发现。哺乳动物中D-氨基酸的出现挑战了生物学中的经典观念，在生物学中只有L-氨基酸会被认为或起着重要作用。最近的发现揭示了内源性D-丝氨酸作为胶质细胞衍生的递质的作用，它调节哺乳动物脑中的谷氨酸能神经传递。脑中游离D-丝氨酸水平约为L-丝氨酸值的三分之一，其细胞外浓度高于许多常见的L-氨基酸。 D-丝氨酸存在于原生质体星形胶质细胞中，这是一类神经胶质细胞，包裹突触并调节神经元活性。生化和电生理研究表明，内源性D-丝氨酸是NMDA型谷氨酸受体共激动剂位点的生理调节剂。我们以前显示D-丝氨酸是由神经胶质丝氨酸消旋酶合成的，神经胶质丝氨酸消旋酶是一种在哺乳动物脑中将L-转化为D-丝氨酸的新型酶。该酶需要吡ido醛5'-磷酸，这是从真核生物中克隆的第一个消旋酶。丝氨酸消旋酶抑制剂对发生NMDA受体过度刺激的病理过程具有治疗意义，例如中风和神经退行性疾病。在这里，我们审查内源性D-丝氨酸在调节NMDA神经传递中的作用，其生物合成装置以及丝氨酸消旋酶抑制剂作为减少谷氨酸/ NMDA兴奋性毒性的新型神经保护策略的潜在作用。

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