Mammalian D-cysteine: A novel regulator of neural progenitor cell proliferation Endogenous D-cysteine, the stereoisomer with rapid spontaneous in vitro racemization rate, has major neural roles
Mammalian D-cysteine: A novel regulator of neural progenitor cell proliferation Endogenous D-cysteine, the stereoisomer with rapid spontaneous in vitro racemization rate, has major neural roles
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DOI：
10.1002/bies.202200002
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发表时间：
2022-04-28
期刊：
影响因子：
4
通讯作者：
Snyder, Solomon H.
中科院分区：
文献类型：
--
作者：
Roychaudhuri, Robin;Snyder, Solomon H.
D-氨基酸被认为是哺乳动物中功能重要的分子。我们最近发现内源性D-半胱氨酸在哺乳动物的大脑。D-半胱氨酸存在于新生儿大脑中的大量（mM），并随着出生后的发育而减少。D-半胱氨酸与MARCKS和一系列与细胞分裂和神经发育障碍有关的蛋白质结合。D-半胱氨酸降低神经祖细胞（NPC）中MARCKS的磷酸化，影响其转位。D-半胱氨酸通过抑制AKT信号传导控制NPC增殖。外源性D-半胱氨酸抑制NPC中Thr 308和Ser 473的AKT磷酸化。D-半胱氨酸处理NPC导致Foxo 1在Ser 256和Foxo 3a在Ser 253的磷酸化减少50%。我们推测，在发育中的脑内源性D-半胱氨酸是作为一个生理调节NPC增殖通过抑制AKT信号转导介导的Foxo 1和Foxo 3a。内源性D-半胱氨酸可调节哺乳动物神经发育，在精神分裂症和阿尔茨海默病（AD）中发挥作用。
D-amino acids are being recognized as functionally important molecules in mammals. We recently identified endogenous D-cysteine in mammalian brain. D-cysteine is present in neonatal brain in substantial amounts (mM) and decreases with postnatal development. D-cysteine binds to MARCKS and a host of proteins implicated in cell division and neurodevelopmental disorders. D-cysteine decreases phosphorylation of MARCKS in neural progenitor cells (NPCs) affecting its translocation. D-cysteine controls NPC proliferation by inhibiting AKT signaling. Exogenous D-cysteine inhibits AKT phosphorylation at Thr 308 and Ser 473 in NPCs. D-cysteine treatment of NPCs led to 50% reduction in phosphorylation of Foxo1 at Ser 256 and Foxo3a at Ser 253. We hypothesize that in the developing brain endogenous D-cysteine is as a physiologic regulator of NPC proliferation by inhibiting AKT signaling mediated by Foxo1 and Foxo3a. Endogenous D-cysteine may regulate mammalian neurodevelopment with roles in schizophrenia and Alzheimer's disease (AD).