Lipid signaling in neural plasticity, brain repair, and neuroprotection
Lipid signaling in neural plasticity, brain repair, and neuroprotection
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DOI：
10.1385/mn:32:1:089
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发表时间：
2005-08-01
影响因子：
5.1
通讯作者：
Bazan, NG
中科院分区：
文献类型：
--
作者：
Bazan, NG
神经系统细胞的广泛网络导致大的细胞膜表面积。我们现在知道，神经元膜含有磷脂库，这些磷脂库是神经元刺激或损伤时合成特定脂质信使的储存库。这些信使反过来参与信号级联，可以促进神经元损伤或神经保护。前列腺素的合成是环氧合酶活性的结果。在花生四烯酸级联反应的第一步中，合成了短寿命的前体前列腺素H2。级联反应中的其他步骤导致合成一系列参与许多生理和神经过程的野牡丹素。我们的实验室最近报道，膜多不饱和脂肪酸，二十二碳六烯酸，是氧合产物的前体，现在被称为二十二烷类化合物，其中一些是强大的抗炎介质。介质10，17 S-二十二碳三烯（神经保护素D1，NPD 1）抵消白细胞浸润，NF-κ活化，并在脑缺血-再灌注的促炎基因表达，是一种抗肿瘤介质，有效地抵消氧化应激引发的视网膜色素上皮细胞凋亡DNA损伤。NPD 1还上调抗凋亡蛋白Bc 1 -2和Bc 1-xL，并降低促凋亡Bax和Bad表达。另一种响应突触活性而衍生自膜磷脂的生物活性信使是血小板活化因子（PAF）。PAF的合成（通过磷脂酶）和降解（通过乙酰水解酶）之间的平衡的严格调节调节这种脂质信使的功能。在病理条件下，这种平衡被打破，PAF成为促炎介质和神经毒性剂。新发现的二十二碳六烯酸信号通路，以及其他与突触激活相关的脂质信使，可能会导致澄清与中风，年龄相关性黄斑变性，脊髓损伤，阿尔茨海默病和其他疾病相关的临床问题，包括神经炎症成分。
The extensive networking of the cells of the nervous system results in large cell membrane surface areas. We now know that neuronal membranes contain phospholipid pools that are the reservoirs for the synthesis of specific lipid messengers on neuronal stimulation or injury. These messengers in turn participate in signaling cascades that can either promote neuronal injury or neuroprotection. Prostaglandins are synthesized as a result of cyclooxygenase activity. In the first step of the arachidonic acid cascade, the short-lived precursor, prostaglandin H2, is synthesized. Additional steps in the cascade result in the synthesis of an array of prostaglandins, which participate in numerous physiological and neurological processes. Our laboratory recently reported that the membrane polyunsaturated fatty acid, docosahexaenoic acid, is the precursor of oxygenation products now known as the docosanoids, some of which are powerful counter-proinflammatory mediators. The mediator 10,17S-docosatriene (neuroprotectin D1, NPD1) counteracts leukocyte infiltration, NF-kappa activation, and proinflammatory gene expression in brain ischemia-reperfusion and is an apoptostatic mediator, potently counteracting oxidative stress-triggered apoptotic DNA damage in retinal pigment epithelial cells. NPD1 also upregulates the anti-apoptotic proteins Bc1-2 and Bc1-xL and decreases pro-apoptotic Bax and Bad expression. Another biologically active messenger derived from membrane phospholipids in response to synaptic activity is platelet-activating factor (PAF). The tight regulation of the balance between synthesis (via phospholipases) and degradation (via acetylhydrolases) of PAF modulates the functions of this lipid messenger. Under pathological conditions, this balance is tipped, and PAF becomes a proinflammatory mediator and neurotoxic agent. The newly discovered docosahexaenoic acid signaling pathways, as well as other lipid messengers related to synaptic activation, may lead to the clarification of clinical issues relevant to stroke, age-related macular degeneration, spinal cord injury, Alzheimer's disease, and other diseases that include neuroinflammatory components.