Diagnostic and therapeutic potentials of exosomes in CNS diseases.
Diagnostic and therapeutic potentials of exosomes in CNS diseases.
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DOI：
10.1016/j.brainres.2014.09.070
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发表时间：
2015-08-18
期刊：
影响因子：
2.9
通讯作者：
Askenase PW
中科院分区：
文献类型：
--
作者：
Kawikova I;Askenase PW
一种新发现的细胞间通讯系统涉及被称为外体的小的、被膜包裹的纳米卵泡。我们在这里描述了这些细胞外纳米颗粒是如何被发现的，以及它们是如何逐渐变得明显的，它们在调节生理功能和病理过程中发挥着基本的作用。胞外体通过将遗传物质、蛋白质和脂类输送到其附近或远处的细胞，从而调节靶细胞的功能，从而实现细胞间的交流。最近的实验表明，外切体也可以由中枢神经系统细胞释放，包括皮质和海马神经元、神经胶质细胞、星形胶质细胞和少突胶质细胞，并且外切体对大脑的病理生理有重要影响。如何决定单个外显子将携带什么到他们的目标还不清楚，但似乎内容物可能代表了根据不同条件而具有特征的“签名货物”。对这些特征的探索可能导致发现新的诊断生物标记物。外切体作为微小RNA或其他化合物的治疗性递送载体也很有希望。如何将外切体运送到选定的地点一直是一个诱人的问题。最近的实验表明，至少有一些外切体在其表面携带抗体，这表明基于这些抗体对抗原的识别，将外切体输送到独特的位置可能是可行的。这一发现意味着，对天然和工程外切体进行相当精确的靶向可能是可行的。这将减少治疗药物的分配量，从而将其副作用降至最低。
A newly discovered cell-to-cell communication system involves small, membrane-enveloped nanovesicles, called exosomes. We describe here how these extracellular nanoparticles were discovered and how it became gradually apparent that they play fundamental roles in regulation of physiological functions and pathological processes. Exosomes enable intercellular communication by transporting genetic material, proteins and lipids to cells in their vicinity or at distant sites, and subsequently regulating functions of targeted cells. Relatively recent experiments indicate that exosomes are released also by CNS cells, including cortical and hippocampal neurons, glial cells, astrocytes and oligodendrocytes, and that exosomes have significant impact on pathophysiology of the brain. How it is decided what individual exosomes will carry to their targets is not understood, but it appears that the contents may represent “signature cargos” that are characteristic for various conditions. Exploration of such characteristics could result in discovery of novel diagnostic biomarkers. Exosomes are also promising as a vehicle for therapeutic delivery of micro RNA or other compounds. How to deliver exosomes to selected sites has been a tantalizing question. Recent experiments revealed that at least some exosomes carry antibodies on their surface, suggesting that it may be feasible to deliver exosomes to unique sites based on the recognition of antigens by those antibodies. This discovery implies that rather precise targeting of both natural and engineered exosomes may be feasible. This would reduce distribution volume of therapeutics, and consequently minimize their side effects.