Thoughts on the role of endogenous D-cysteine in neuronal function.
Thoughts on the role of endogenous D-cysteine in neuronal function.
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DOI：
10.1002/bies.202200089
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发表时间：
2022-07
期刊：
影响因子：
4
通讯作者：
Seckler, James M.
中科院分区：
文献类型：
--
作者：
Seckler, James M.
D-半胱氨酸是大脑中一种未被充分研究和低估的内源氨基酸。由于其检测困难，多年来它在神经元功能中的作用一直未被充分研究。最近的研究表明，D-半胱氨酸和细胞渗透性衍生物（例如 D-半胱氨酸乙酯）在神经祖细胞增殖和逆转阿片类药物引起的呼吸抑制中发挥作用。这些最近的研究，再加上D-半胱氨酸在体内受到D-氨基酸氧化酶高度调节的证据以及可能的其他机制，表明它是体内的一种活性氨基酸，可能参与多种疾病模型。半胱氨酸的D-异构体（D-半胱氨酸）是体内受到严格调节的化学物质。 D-半胱氨酸虽然很容易在肠道中吸收，但会被 D-氨基酸氧化酶 (DAO) 和 3-巯基丙酮酸硫转移酶 (3MS) 的组合快速降解为硫化氢[1]。研究表明，尽管 D-丝氨酸在大脑中更为普遍，但 D-半胱氨酸是 DAO 的主要底物 [1]。正是由于这种严格的调控，直到最近才发现 D-半胱氨酸是由丝氨酸消旋酶 (SR) 在大脑中内源产生的[2]。 D-半胱氨酸水平在产前大脑中最高，并随着年龄的增长而迅速下降[2]。 DAO 表达在人类产前大脑中极低，并随着年龄的增长而增加，在生命的头两年显着增加[3]。早期大脑发育似乎需要高水平的 D-半胱氨酸，事实上，Roychaudhuri 和 Snyder 出色地提出了 D-半胱氨酸如何通过改变激酶信号传导来调节细胞增殖的假设 [2]。然而，内源性 D-半胱氨酸是否在正常脑功能中发挥作用仍然是一个问题。
D-Cysteine is an understudied and underappreciated endogenous amino acid in the brain. Its role in neuronal function has been understudied for years due to the difficulty in detecting it. There is recent work showing that D-cysteine and cell permeable derivatives such as D-cysteine ethyl ester play a role in neural progenitor cell proliferation and reversing opioid induced respiratory depression. These recent studies, coupled with evidence that D-cysteine is highly regulated in the body by D-amino acid oxidase and possibly other mechanisms suggest that it is an active amino acid in the body, which could be involved in a variety of disease models.The D-isomer of cysteine (D-cysteine) is a tightly regulated chemical in the body. While readily absorbed in the gut, D-cysteine is rapidly degraded to hydrogen sulfide by a combination of D-amino acid oxidase (DAO) and 3-mercaptopyruvate sulfurtransferase (3MS)[1]. It has been shown that D-cysteine is the primary substrate of DAO, even though D-serine is more prevalent in the brain [1]. It was due to this tight regulation that it was only recently discovered that D-cysteine is endogenously produced in the brain by Serine Racemase (SR)[2]. D-cysteine levels are highest in prenatal brain and rapidly decline with age [2]. DAO expression is extremely low in pre-natal brains of humans, and increases with age, rising significantly in the first two years of life [3]. It would seem that high levels of D-cysteine are required for early brain development, and indeed Roychaudhuri and Snyder do an excellent job of laying out a hypothesis for how D-Cysteine regulates cell proliferation by altering kinase signaling [2]. However, the question remains as to whether endogenous D-Cysteine plays a role in normal brain function.
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影响因子：
2.3
作者：
Getsy, Paulina M.;Young, Alex P.;Grossfield, Alan;Seckler, James M.;Wilson, Christopher G.;Gaston, Benjamin;Bates, James N.;Lewis, Stephen J.
通讯作者：
Lewis, Stephen J.
影响因子：
5
作者：
Sacchi S;Cappelletti P;Murtas G
通讯作者：
Murtas G
影响因子：
4
作者：
Roychaudhuri, Robin;Snyder, Solomon H.
通讯作者：
Snyder, Solomon H.
影响因子：
2.9
作者：
Jagannath V;Marinova Z;Monoranu CM;Walitza S;Grünblatt E
通讯作者：
Grünblatt E
影响因子：
5.6
作者：
Seckler JM;Lewis SJ
通讯作者：
Lewis SJ