University Department of Clinical Neurosciences, Institute of Neurology, University College London, UK.
Neurobiol Dis. 2011 Jun;42(3):360-7. doi: 10.1016/j.nbd.2011.01.029. Epub 2011 Feb 18.
Alpha-synuclein aggregation plays a central role in Parkinson's disease pathology. Direct transmission of alpha-synuclein from pathologically affected to healthy unaffected neurons may be important in the anatomical spread of the disease through the nervous system. We have demonstrated that exosomes released from alpha-synuclein over-expressing SH-SY5Y cells contained alpha-synuclein and these exosomes were capable of efficiently transferring alpha-synuclein protein to normal SH-SY5Y cells. Moreover, the incubation of cells with ammonium chloride or bafilomycin A1 to produce the lysosomal dysfunction recently reported in Parkinson's disease led to an increase in the release of alpha-synuclein in exosomes and a concomitant increase in alpha-synuclein transmission to recipient cells. This study clearly demonstrates the importance of exosomes in both the release of alpha synuclein and its transmission between cells and suggests that factors associated with PD pathology accelerate this process. These mechanisms may play an important role in PD pathology and provide a suitable target for therapeutic intervention.
α-突触核蛋白聚集在帕金森病病理学中起着核心作用。从病变影响到健康未受影响的神经元的α-突触核蛋白的直接传递，可能在疾病通过神经系统的解剖传播中很重要。我们已经证明，来自过度表达α-突触核蛋白的 SH-SY5Y 细胞释放的外体含有α-突触核蛋白，并且这些外体能够有效地将α-突触核蛋白蛋白转移到正常的 SH-SY5Y 细胞中。此外，用氯化铵或巴弗洛霉素 A1 孵育细胞以产生最近在帕金森病中报道的溶酶体功能障碍，导致外体中α-突触核蛋白的释放增加，并伴随着向受体细胞传递α-突触核蛋白的增加。这项研究清楚地表明了外体在α-突触核蛋白的释放及其在细胞间传递中的重要性，并表明与 PD 病理学相关的因素加速了这一过程。这些机制可能在 PD 病理学中起重要作用，并为治疗干预提供了合适的靶点。
