MiRNAs in Astrocyte-Derived Exosomes as Possible Mediators of Neuronal Plasticity.

MiRNAs in Astrocyte-Derived Exosomes as Possible Mediators of Neuronal Plasticity.
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DOI:
10.4137/jen.s39916
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发表时间:
2016
影响因子:
--
通讯作者:
Wyneken U
Wyneken U
中科院分区:
其他
文献类型:
--
作者:
Lafourcade C;Ramírez JP;Luarte A;Fernández A;Wyneken U

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星形胶质细胞使用胶质递质来调节神经元的功能和可塑性。然而,小的细胞外囊泡,称为外泌体,在星形胶质细胞到神经元信号传导中的作用大多是未知的。外泌体起源于亲本细胞的多泡体,并且通过多泡体限制膜与质膜的融合而分泌。它们的分子货物由RNA种类、蛋白质和脂质组成,部分是细胞类型和细胞状态特异性的。在由外来体转运的RNA种类中,微小RNA(miRNA)能够修饰受体细胞中的基因表达。存在于星形胶质细胞中的几种miRNA在病理条件下受到调节,如果它们被加载到外泌体中,这可能会产生深远的影响。我们提出,星形胶质细胞衍生的miRNA负载的外泌体,如miR-26 a,在几种中枢神经系统疾病中失调;因此,通过验证和预测的靶点,可能控制神经元形态和突触传递。揭示这种新的信号机制对神经网络的维持和可塑性的贡献将影响我们对中枢神经系统生理学和病理生理学的理解。
Astrocytes use gliotransmitters to modulate neuronal function and plasticity. However, the role of small extracellular vesicles, called exosomes, in astrocyte-to-neuron signaling is mostly unknown. Exosomes originate in multivesicular bodies of parent cells and are secreted by fusion of the multivesicular body limiting membrane with the plasma membrane. Their molecular cargo, consisting of RNA species, proteins, and lipids, is in part cell type and cell state specific. Among the RNA species transported by exosomes, microRNAs (miRNAs) are able to modify gene expression in recipient cells. Several miRNAs present in astrocytes are regulated under pathological conditions, and this may have far-reaching consequences if they are loaded in exosomes. We propose that astrocyte-derived miRNA-loaded exosomes, such as miR-26a, are dysregulated in several central nervous system diseases; thus potentially controlling neuronal morphology and synaptic transmission through validated and predicted targets. Unraveling the contribution of this new signaling mechanism to the maintenance and plasticity of neuronal networks will impact our understanding on the physiology and pathophysiology of the central nervous system.