Glucocerebrosidase depletion enhances cell-to-cell transmission of α-synuclein.
Glucocerebrosidase depletion enhances cell-to-cell transmission of α-synuclein.
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DOI：
10.1038/ncomms5755
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发表时间：
2014-08-26
影响因子：
16.6
通讯作者：
Lee, Seung-Jae
中科院分区：
文献类型：
--
作者：
Bae, Eun-Jin;Yang, Na-Young;Song, Miyoung;Lee, Cheol Soon;Lee, Jun Sung;Jung, Byung Chul;Lee, He-Jin;Kim, Seokjoong;Masliah, Eliezer;Sardi, Sergio Pablo;Lee, Seung-Jae
α-突触核蛋白聚集体沉积广泛存在于帕金森病(PD)的中枢和外周神经系统。尽管最近的证据表明α-突触核蛋白聚集体的细胞间传递推动了帕金森病的进展，但α-突触核蛋白聚集体扩散的机制仍然不清楚。在这里，我们表明α-突触核蛋白聚集体是通过一个连续的循环传递的，包括摄取外部聚集体，与内源α-突触核蛋白共聚集，以及共聚体的胞吐。此外，我们发现葡萄糖脑苷酶耗竭，以前一直与帕金森病和认知损伤增加密切相关，促进了α-突触核蛋白聚集体的繁殖。这些研究定义了α-突触核蛋白聚集体如何在神经细胞中扩散，并解释了葡萄糖脑苷酶突变如何增加发展为帕金森病和其他突触核病的风险。
Deposition of α-synuclein aggregates occurs widely in the central and peripheral nervous systems in Parkinson’s disease (PD). Although recent evidence has suggested that cell-to-cell transmission of α-synuclein aggregates drives the progression of PD, the mechanism by which α-synuclein aggregates spread remains undefined. Here, we show that α-synuclein aggregates are perpetually transmitted through a continuous cycle involving uptake of external aggregates, co-aggregation with endogenous α-synuclein, and exocytosis of the co-aggregates. Moreover, we found that glucocerebrosidase depletion, which has previously been strongly associated with PD and increased cognitive impairment, promoted propagation of α-synuclein aggregates. These studies define how α-synuclein aggregates spread among neuronal cells and explain how glucocerebrosidase mutations increase the risk of developing PD and other synucleinopathies.
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影响因子：
9.9
作者：
Alcalay, R. N.;Caccappolo, E.;Marder, K.
通讯作者：
Marder, K.
影响因子：
3.5
作者：
Ron, I;Horowitz, M
通讯作者：
Horowitz, M
影响因子：
15.1
作者：
Danzer KM;Kranich LR;Ruf WP;Cagsal-Getkin O;Winslow AR;Zhu L;Vanderburg CR;McLean PJ
通讯作者：
McLean PJ
影响因子：
3.7
作者：
Angot E;Steiner JA;Lema Tomé CM;Ekström P;Mattsson B;Björklund A;Brundin P
通讯作者：
Brundin P
影响因子：
29
作者：
Nalls, Michael A.;Duran, Raquel;Sidransky, Ellen
通讯作者：
Sidransky, Ellen