Molecular and Signaling Mechanisms for Docosahexaenoic Acid-Derived Neurodevelopment and Neuroprotection.
Molecular and Signaling Mechanisms for Docosahexaenoic Acid-Derived Neurodevelopment and Neuroprotection.
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DOI：
10.3390/ijms23094635
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发表时间：
2022-04-22
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
二十二碳六烯酸 (DHA) 的神经发育和神经保护作用是通过涉及膜和代谢物相关信号转导的机制介导的。 DHA 膜介导作用的一个关键特征是刺激神经元磷脂酰丝氨酸 (PS) 的合成。由此产生的富含 DHA-PS 的膜结构域促进 Raf-1、蛋白激酶 C (PKC) 和 Akt 等激酶的易位和激活。这些信号通路的激活促进神经元的发育和存活。 DHA 也在神经组织中代谢为生物活性介质。神经保护素 D1 是一种由脂氧合酶活性合成的二十二碳三烯，具有抗炎特性，而由 DHA 延伸产物形成的 elovanoids 在视网膜中表现出抗氧化作用。 Synaptamide 是一种由 DHA 在大脑中合成的内源性大麻素样脂质介质，可促进神经发生和突触发生，并发挥抗炎作用。它与 GPR110 (ADGRF1) 受体的 GAIN 结构域结合，触发 cAMP/蛋白激酶 A (PKA) 信号通路，并激活 cAMP 反应元件结合蛋白 (CREB)。大脑中的 DHA 状态不仅影响 PS 依赖性信号转导，还影响 CREB 下游并影响神经传递的突触前和突触后蛋白质的代谢物形成和表达。这些过程的综合作用有助于 DHA 的神经发育和神经保护作用。
The neurodevelopmental and neuroprotective actions of docosahexaenoic acid (DHA) are mediated by mechanisms involving membrane- and metabolite-related signal transduction. A key characteristic in the membrane-mediated action of DHA results from the stimulated synthesis of neuronal phosphatidylserine (PS). The resulting DHA-PS-rich membrane domains facilitate the translocation and activation of kinases such as Raf-1, protein kinase C (PKC), and Akt. The activation of these signaling pathways promotes neuronal development and survival. DHA is also metabolized in neural tissues to bioactive mediators. Neuroprotectin D1, a docosatriene synthesized by the lipoxygenase activity, has an anti-inflammatory property, and elovanoids formed from DHA elongation products exhibit antioxidant effects in the retina. Synaptamide, an endocannabinoid-like lipid mediator synthesized from DHA in the brain, promotes neurogenesis and synaptogenesis and exerts anti-inflammatory effects. It binds to the GAIN domain of the GPR110 (ADGRF1) receptor, triggers the cAMP/protein kinase A (PKA) signaling pathway, and activates the cAMP-response element binding protein (CREB). The DHA status in the brain influences not only the PS-dependent signal transduction but also the metabolite formation and expression of pre- and post-synaptic proteins that are downstream of the CREB and affect neurotransmission. The combined actions of these processes contribute to the neurodevelopmental and neuroprotective effects of DHA.
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影响因子：
13.6
作者：
Kim, Hee-Yong;Huang, Bill X.;Spector, Arthur A.
通讯作者：
Spector, Arthur A.
DOI：
10.1074/jbc.r117.783076
发表时间：
2017-07-28
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Asatryan A;Bazan NG
通讯作者：
Bazan NG
影响因子：
2.4
作者：
Kharebava, Giorgi;Rashid, Mohammad A.;Kim, Hee-Yong
通讯作者：
Kim, Hee-Yong
影响因子：
6.5
作者：
Jin J;Boeglin WE;Brash AR
通讯作者：
Brash AR
影响因子：
5.9
作者：
Huang, Bill X.;Hu, Xin;Kim, Hee-Yong
通讯作者：
Kim, Hee-Yong