Departments of Medicine and Biomedical Sciences, Neuroscience Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongro-gu, Seoul, 03080, South Korea.
Acta Neuropathol Commun. 2017 Aug 29;5(1):64. doi: 10.1186/s40478-017-0467-z.
Abnormal protein aggregation has been implicated in neurodegenerative processes in human neurological disorders, such as Alzheimer's disease and Parkinson's disease. Recently, studies have established a novel concept that protein aggregates are transmitted among neuronal cells. By extension, such interneuronal aggregate transmission has been hypothesized to be the underlying mechanism for the pathological and clinical disease progression. However, the precise mechanism of the interneuronal aggregate transmission remains ill-defined. Recent reports have suggested that exosomes, a specific group of extracellular vesicles that are involved in intercellular transfer of cellular macromolecules such as proteins and RNAs, could play an important role in the aggregate transmission among neurons. Here, we review various types of extracellular vesicles and critically evaluate the evidence supporting the role of exosomes in interneuronal aggregate transmission and neurodegeneration. We also discuss the competing mechanisms other than the exosome-mediated transmission. By doing so, we aim to assess the current state of knowledge on the mechanism of interneuronal aggregate transmission and suggest the future directions of research towards understanding the mechanism.
异常蛋白质聚集与人类神经紊乱中的神经退行性过程有关，如阿尔茨海默病和帕金森病。最近的研究确立了一个新的概念，即蛋白质聚集体在神经元细胞之间传递。由此推断，这种神经元间的聚集体传递可能是导致病理和临床疾病进展的潜在机制。然而，神经元间聚集体传递的确切机制仍不清楚。最近的报告表明，外泌体作为一种特定的细胞外囊泡，参与细胞内大分子如蛋白质和 RNA 的细胞间转移，在外泌体在神经元之间的聚集体传递中可能发挥重要作用。在这里，我们综述了各种类型的细胞外囊泡，并批判性地评估了支持外泌体在神经元间聚集体传递和神经退行性变中的作用的证据。我们还讨论了除外泌体介导的传递之外的竞争机制。通过这样做，我们旨在评估目前对神经元间聚集体传递机制的认识，并为理解该机制提出未来的研究方向。
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