Docosanoids are multifunctional regulators of neural cell integrity and fate: Significance in aging and disease
Docosanoids are multifunctional regulators of neural cell integrity and fate: Significance in aging and disease
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DOI：
10.1016/j.plefa.2007.10.022
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发表时间：
2007-11-01
影响因子：
3
通讯作者：
Bazan, N. G.
中科院分区：
文献类型：
--
作者：
Kherjee, P. K. Mu.;Chawla, A.;Bazan, N. G.
神经保护素D1（NPD 1）是二十二碳六烯酸（DHA）在脑和视网膜中的生物合成产物，其生物活性的鉴定和表征使人们对omega-3脂肪酸在中枢神经系统中的功能作用和病理生理学意义产生了新的兴趣。神经营养因子，特别是色素上皮衍生因子（PEDF），诱导NPD 1的合成及其极化顶端分泌，这意味着这种脂质介质的旁分泌和自分泌生物活性。此外，DHA和PEDF协同激活NPD 1合成和抗凋亡蛋白表达，并降低氧化应激过程中促凋亡Bcl-2蛋白表达和caspase 3激活。并且在这些条件下将脂质介质输注到脑中揭示了NPD 1的神经保护生物活性。DHA衍生的神经保护信号的相互作用旨在抵消由多种会聚的细胞因子和淀粉样肽因子触发的促炎性细胞损伤事件，如在AD的情况下。因此，从DHA产生NPD 1似乎将细胞命运重定向到成功保存视网膜色素上皮（RPE）-感光细胞完整性和脑细胞老化。Bcl-2促凋亡蛋白和抗凋亡蛋白、神经营养因子和NPD 1沿着细胞命运调节途径，其组分成员高度相互作用，并具有在细胞存活中协同发挥作用的潜力。刺激NPD 1生物合成的试剂、NPD 1类似物或饮食方案可用作神经退行性疾病的新的预防/治疗策略。(C)2007爱思唯尔有限公司保留所有权利。
The identification of neuroprotectin D1 (NPD1), a biosynthetic product of docosahexaenoic acid (DHA), in brain and retina as well as the characterization of its bioactivity, is generating a renewed interest in the functional role and pathophysiological significance of omega-3 fatty acids in the central nervous system.Neurotrophins, particularly pigment epithelium-derived factor (PEDF), induce NPD1 synthesis and its polarized apical secretion, implying paracrine and autocrine bioactivity of this lipid mediator. Also, DHA and PEDF synergistically activate NPD1 synthesis and antiapoptotic protein expression and decreased proapoptotic Bcl-2 protein expression and caspase 3 activation during oxidative stress.In experimental stroke, endogenous NPD1 synthesis was found to be upregulated, and the infusion of the lipid mediator into the brain under these conditions revealed neuroprotective bioactivity of NPD1.The hippocampal CA1 region from Alzheimer's disease (AD) patients (rapidly sampled) shows a major reduction in NPD1.The interplay of DHA-derived neuroprotective signaling aims to counteract proinflammatory, cell-damaging events triggered by multiple, converging cytokine and amyloid peptide factors, as in the case of AD. Generation of NPD1 from DHA thereby appears to redirect cellular fate toward successful preservation of retinal pigment epithelial (RPE)-photoreceptor cell integrity and brain cell aging. The Bcl-2 pro- and antiapoptotic proteins, neurotrophins, and NPD1, lie along a cell fate-regulatory pathway whose component members are highly interactive, and have potential to function cooperatively in cell survival. Agents that stimulate NPD1 biosynthesis, NPD1 analogs, or dietary regimens may be useful as new preventive/therapeutic strategies for neurodegenerative diseases. (C) 2007 Elsevier Ltd. All rights reserved.