Port-to-port delivery: Mobilization of toxic sphingolipids via extracellular vesicles.
Port-to-port delivery: Mobilization of toxic sphingolipids via extracellular vesicles.
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DOI：
10.1002/jnr.23798
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发表时间：
2016-11
影响因子：
4.2
通讯作者：
Givogri, Maria I.
中科院分区：
文献类型：
--
作者：
Scesa, Giuseppe;Moyano, Ana Lis;Bongarzone, Ernesto R.;Givogri, Maria I.
大多数细胞产生细胞外囊泡（EV）并将其释放到细胞外环境中的发现激发了这些膜货物传播致病机制的想法。在大脑中，EV可能具有多重和重要的生理功能，从解除突触活性调节，到促进脱髓鞘，再到小胶质细胞活性的变化。小EV（外泌体）含有α-突触核蛋白和β-淀粉样蛋白等致病蛋白的发现是这一概念的一个例子，强调了它们在帕金森病和阿尔茨海默病患者大脑中的潜在作用。作为膜囊泡，我们推测EV也具有并入鞘脂的内在能力。在这些脂质升高至毒性水平的情况下，例如在Krabbe病和异染性脑白质营养不良中，EV可能有助于将疾病从患病细胞传播到健康细胞。在这篇文章中，我们讨论了一个工作假设，即脑细胞在鞘脂清除一些积累的脂质物质，试图通过EV分泌恢复细胞内稳态。我们假设分泌的鞘脂装载的EV将致病脂质穿梭到本质上不受影响的细胞中，有助于建立非细胞自主缺陷。
The discovery that most cells produce extracellular vesicles (EVs) and release them in the extracellular milieu has spurred the idea that these membranous cargoes spread pathogenic mechanisms. In the brain, EVs may have multifold and important physiological functions, from deregulating synaptic activity, to promoting demyelination, to changes in microglial activity. The finding that small EVs (exosomes) contain α-synuclein and β-amyloid, among other pathogenic proteins, is an example of this notion, underlining their potential role in the brain of patients with Parkinson’s and Alzheimer’s diseases. Being membranous-vesicles, we speculate that EVs also have an intrinsic capacity to incorporate sphingolipids. In conditions where these lipids are elevated to toxic levels such as in Krabbe’s disease and Metachromatic leukodystrophy, EVs may contribute to spread disease from sick to healthy cells. In this essay, we discuss a working hypothesis that brain cells in sphingolipidoses clear some of the accumulated lipid material to attempt restoring cell homeostasis via EV secretion. We hypothesize that secreted sphingolipid-loaded EVs shuttle pathogenic lipids to cells that are not intrinsically affected, contributing to establishing non-cell autonomous defects.
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影响因子：
46.9
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
5.9
作者：
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