Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission.
Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission.
复制标题
DOI：
10.1016/j.nbd.2011.01.029
复制
发表时间：
2011-06
影响因子：
6.1
通讯作者：
Cooper, J. Mark
中科院分区：
文献类型：
--
作者：
Alvarez-Erviti, Lydia;Seow, Yiqi;Schapira, Anthony H.;Gardiner, Chris;Sargent, Ian L.;Wood, Matthew J. A.;Cooper, J. Mark
α-突触核蛋白聚集在帕金森病病理学中起着核心作用。α-突触核蛋白从病理影响的神经元直接传递到健康的未受影响的神经元可能在疾病通过神经系统的解剖学传播中是重要的。我们已经证明，从α-突触核蛋白过表达的SH-SY 5 Y细胞释放的外泌体含有α-突触核蛋白，并且这些外泌体能够有效地将α-突触核蛋白转移到正常的SH-SY 5 Y细胞。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，导致外泌体中α-突触核蛋白的释放增加，并伴随着α-突触核蛋白向受体细胞的传递增加。这项研究清楚地证明了外泌体在α突触核蛋白的释放及其在细胞之间的传递中的重要性，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病理学中发挥重要作用，并为治疗干预提供合适的靶点。从细胞释放的外泌体含有α-突触核蛋白。Exosomes在细胞间传递α-synuclein蛋白。帕金森病中发现的溶酶体缺陷增加了外泌体α-突触核蛋白的释放。溶酶体功能障碍增加了外泌体介导的α-突触核蛋白转移。
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. ► Exosomes released from cells contain α-synuclein. ► Exosomes transfer α-synuclein protein between cells. ► Lysosomal defects seen in Parkinson's disease increase exosomal α-synuclein release. ► Lysosomal dysfunction increases α-synuclein transfer mediate by exosomes.
登录
查看更多内容
影响因子：
6.1
作者：
Chu, Yaping;Dodiya, Hemraj;Kordower, Jeffrey H.
通讯作者：
Kordower, Jeffrey H.
影响因子：
--
作者：
Alvarez-Erviti, Lydia;Rodriguez-Oroz, Maria C.;Schapira, Anthony H. V.
通讯作者：
Schapira, Anthony H. V.
DOI：
10.1073/pnas.0308413101
发表时间：
2004-06-29
影响因子：
11.1
作者：
Fevrier, B;Vilette, D;Raposo, G
通讯作者：
Raposo, G
影响因子：
5.3
作者：
Emmanouilidou, Evangelia;Melachroinou, Katerina;Vekrellis, Kostas
通讯作者：
Vekrellis, Kostas
影响因子：
4.7
作者：
Chau, Kai-Yin;Ching, Hey Long;Cooper, J. Mark
通讯作者：
Cooper, J. Mark