Endogenous signaling by omega-3 docosahexaenoic acid-derived mediators sustains homeostatic synaptic and circuitry integrity.
Endogenous signaling by omega-3 docosahexaenoic acid-derived mediators sustains homeostatic synaptic and circuitry integrity.
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DOI：
10.1007/s12035-011-8200-6
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发表时间：
2011-10
影响因子：
5.1
通讯作者：
Knott, Eric J.
中科院分区：
文献类型：
--
作者：
Bazan, Nicolas G.;Musto, Alberto E.;Knott, Eric J.
复杂的脑回路和突触的协调和功能主要由兴奋性和抑制性神经传递、神经营养因子、基因调节和因子维持，其中许多因子尚未完全理解。脑回路成分的一个共同特征，如树突、突触膜和神经系统的其他膜，是它们富含二十二碳六烯酸（DHA），这是ω-3必需脂肪酸家族的主要成员。DHA在神经系统中被大量保留和浓缩，已知在神经保护、记忆和视力方面发挥作用。直到最近，人们才明白为什么在癫痫发作或脑损伤时游离（未酯化）DHA库的大小会惊人地迅速增加。这种现象开始被神经保护素D1（NPD 1）的发现所澄清，NPD 1是第一个发现的生物活性二十二烷类化合物，由游离DHA通过15-脂氧合酶-1（15-LOX-1）形成。NPD 1合成包括作为激动剂的氧化应激和神经营养因子。不断发展的概念是DHA衍生的二十二烷类化合物启动内源性信号传导以维持稳态突触和回路的完整性。NPD 1是抗炎的，显示炎症消退活性，并诱导细胞存活，这与许多ω-6脂肪酸家族成员的促炎作用相反。我们在这里强调的DHA信号脂质组学的背景下，DHA维持神经元功能和保护突触和电路的能力相关的研究。DHA信号脂质组学包括DHA摄取的细胞/组织机制、其在细胞区室中的分布、含有DHA磷脂的膜结构域的组织和功能以及通过揭示被赋予促稳态和细胞存活生物活性的二十二烷类化合物调节的信号通路所揭示的精确的细胞和分子事件的整合。因此，这种方法为预防、药物干预和涉及DHA介导的信号传导的临床翻译提供了新的靶点。
The harmony and function of the complex brain circuits and synapses are sustained mainly by excitatory and inhibitory neurotransmission, neurotrophins, gene regulation, and factors, many of which are incompletely understood. A common feature of brain circuit components, such as dendrites, synaptic membranes, and other membranes of the nervous system, is that they are richly endowed in docosahexaenoic acid (DHA), the main member of the omega-3 essential fatty acid family. DHA is avidly retained and concentrated in the nervous system and known to play a role in neuroprotection, memory, and vision. Only recently has it become apparent why the surprisingly rapid increases in free (unesterified) DHA pool size take place at the onset of seizures or brain injury. This phenomenon began to be clarified by the discovery of neuroprotectin D1 (NPD1), the first-uncovered bioactive docosanoid formed from free DHA through 15-lipoxygenase-1 (15-LOX-1). NPD1 synthesis includes, as agonists, oxidative stress and neurotrophins. The evolving concept is that DHA-derived docosanoids set in motion endogenous signaling to sustain homeostatic synaptic and circuit integrity. NPD1 is anti-inflammatory, displays inflammatory resolving activities, and induces cell survival, which is in contrast to the pro-inflammatory actions of the many of omega-6 fatty acid family members. We highlight here studies relevant to the ability of DHA to sustain neuronal function and protect synapses and circuits in the context of DHA signalolipidomics. DHA signalolipidomics comprises the integration of the cellular/tissue mechanism of DHA uptake, its distribution among cellular compartments, the organization and function of membrane domains containing DHA phospholipids, and the precise cellular and molecular events revealed by the uncovering of signaling pathways regulated by docosanoids endowed with prohomeostatic and cell survival bioactivity. Therefore, this approach offers emerging targets for prevention, pharmaceutical intervention, and clinical translation involving DHA-mediated signaling.
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营养中的Docosahexaenoic酸信号脂肪组学：衰老，神经炎症，黄斑变性，阿尔茨海默氏症和其他神经退行性疾病的重要性。
影响因子：
8.9
作者：
Bazan NG;Molina MF;Gordon WC
通讯作者：
Gordon WC
影响因子：
5.3
作者：
Cole-Edwards, Kasie K.;Musto, Alberto E.;Bazan, Nicolas G.
通讯作者：
Bazan, Nicolas G.
DOI：
10.1073/pnas.0705963104
发表时间：
2007-08-07
影响因子：
11.1
作者：
Mukherjee, Pranab K.;Marcheselli, Victor L.;Bazan, Nicolas G.
通讯作者：
Bazan, Nicolas G.
影响因子：
2.2
作者：
Galasko D;Montine TJ
通讯作者：
Montine TJ
影响因子：
64.8
作者：
Collins, Pamela Y.;Patel, Vikram;Joestl, Sarah S.;March, Dana;Insel, Thomas R.;Daar, Abdallah S.
通讯作者：
Daar, Abdallah S.