Docosahexaenoic acid prevents neuronal apoptosis induced by soluble amyloid-β oligomers
Docosahexaenoic acid prevents neuronal apoptosis induced by soluble amyloid-β oligomers
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DOI：
10.1111/j.1471-4159.2005.03541.x
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发表时间：
2006-01-01
影响因子：
4.7
通讯作者：
Oster, T
中科院分区：
文献类型：
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作者：
Florent, S;Malaplate-Armand, C;Oster, T
越来越多的证据支持这一观点，即淀粉样蛋白 (Aβ) 肽的可溶性低聚物与神经元质膜相互作用，导致细胞损伤并诱导死亡信号通路，这可能是阿尔茨海默病 (AD) 中神经变性加剧的原因。二十二碳六烯酸 (DHA, C22:6, n-3) 是中枢神经系统必需的多不饱和脂肪酸，多项流行病学和体内研究表明，对 AD 和认知改变具有保护作用。然而，所涉及的分子机制仍然未知。我们假设质膜上的 DHA 富集可以保护神经元免受可溶性 Aβ 寡聚体诱导的细胞凋亡。据观察，DHA 预处理可通过防止细胞骨架扰动、半胱天冬酶激活和细胞凋亡以及促进细胞外信号相关激酶 (ERK) 相关存活途径，显着提高 Aβ 治疗后的神经元存活率。这些数据表明，DHA 富集可能会引起神经元膜特性的变化和功能结果，从而增强对可溶性 Aβ 寡聚物的保护。这种神经保护作用可能对预防 AD 和其他神经退行性疾病具有重要意义。
A growing body of evidence supports the notion that soluble oligomers of amyloid-beta (A beta) peptide interact with the neuronal plasma membrane, leading to cell injury and inducing death-signalling pathways that could account for the increased neurodegeneration occurring in Alzheimer's disease (AD). Docosahexaenoic acid (DHA, C22:6, n-3) is an essential polyunsaturated fatty acid in the CNS and has been shown in several epidemiological and in vivo studies to have protective effects against AD and cognitive alterations. However, the molecular mechanisms involved remain unknown. We hypothesized that DHA enrichment of plasma membranes could protect neurones from apoptosis induced by soluble A beta oligomers. DHA pre-treatment was observed to significantly increase neuronal survival upon A beta treatment by preventing cytoskeleton perturbations, caspase activation and apoptosis, as well as by promoting extracellular signal-related kinase (ERK)-related survival pathways. These data suggest that DHA enrichment probably induces changes in neuronal membrane properties with functional outcomes, thereby increasing protection from soluble A beta oligomers. Such neuroprotective effects could be of major interest in the prevention of AD and other neurodegenerative diseases.