The onset of brain injury and neurodegeneration triggers the synthesis of docosanoid neuroprotective signaling
The onset of brain injury and neurodegeneration triggers the synthesis of docosanoid neuroprotective signaling
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DOI：
10.1007/s10571-006-9064-6
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发表时间：
2006-07-01
影响因子：
4
通讯作者：
Bazan, Nicolas G.
中科院分区：
文献类型：
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作者：
Bazan, Nicolas G.
生物活性脂质信使是通过磷脂酶介导的特定磷脂从膜库中裂解而形成的。激活脂质信使合成的效应子包括离子通道、神经递质、膜去极化、细胞因子和神经营养因子。反过来，脂质信使调节多种途径并与之相互作用，参与发育、分化、功能（例如，长期增强和记忆）、保护和修复神经系统细胞。总体而言，生物活性脂质参与调节突触功能和功能障碍。血小板活化因子（PAF）和考克斯-2合成的PGE（2）调节突触可塑性和记忆。氧化应激破坏脂质信号传导，促进脂质过氧化，并引发和传播神经变性。脂质信使参与神经元、星形胶质细胞、少突胶质细胞、小胶质细胞、微血管细胞和其他细胞之间的相互作用。神经血管单位是由相互关联的细胞组成的。在脑血管疾病的早期阶段以及在神经退行性病变中，神经血管单位的信号传导明显改变。在这里，我们将提供如何通过脂质信号调节神经元存活所必需的关键事件的例子。我们将强调一个新发现的，DHA衍生的信使，神经保护素D1，它减弱氧化应激诱导的细胞凋亡。这种新的类二十二烷（神经保护素D1）的特异性和效力表明了治疗干预的潜在重要靶点。
Bioactive lipid messengers are formed through phospholipase-mediated cleavage of specific phospholipids from membrane reservoirs. Effectors that activate the synthesis of lipid messengers, include ion channels, neurotransmitters, membrane depolarization, cytokines, and neurotrophic factors. In turn, lipid messengers regulate and interact with multiple pathways, participating in the development, differentiation, function (e.g., long-term potentiation and memory), protection, and repair of cells of the nervous system. Overall, bioactive lipids participate in the regulation of synaptic function and dysfunction. Platelet-activating factor (PAF) and COX-2-synthesized PGE(2) modulate synaptic plasticity and memory. Oxidative stress disrupts lipid signaling, fosters lipid peroxidation, and initiates and propagates neurodegeneration. Lipid messengers participate in the interactions among neurons, astrocytes, oligodendrocytes, microglia, cells of the microvasculature, and other cells. A conglomerate of interrelated cells comprises the neurovascular unit. Signaling at the neurovascular unit is clearly altered in the early stages of cerebrovascular disease as well as in neurodegenerations. Here we will provide examples of how signaling by lipids regulates critical events essential for neuronal survival. We will highlight a newly identified, DHA-derived messenger, neuroprotectin D1, which attenuates oxidative stress-induced apoptosis. The specificity and potency of this novel docosanoid (neuroprotectin D1) indicate a potentially important target for therapeutic intervention.