Glucocerebrosidase depletion enhances cell-to-cell transmission of α-synuclein

被引：154

作者：

Bae, Eun-Jin ^{[1
]}

Yang, Na-Young ^{[1
]}

Song, Miyoung ^{[1
]}

Lee, Cheol Soon ^{[2
]}

Lee, Jun Sung ^{[1
]}

Jung, Byung Chul ^{[1
,3
]}

Lee, He-Jin ^{[2
]}

Kim, Seokjoong ^{[4
]}

Masliah, Eliezer ^{[5
,6
]}

Sardi, Sergio Pablo ^{[7
]}

Lee, Seung-Jae ^{[1
,8
]}

机构：

[1] Konkuk Univ, Dept Biomed Sci & Technol, Seoul 143701, South Korea

[2] Konkuk Univ, Sch Med, Dept Anat, Seoul 143701, South Korea

[3] Yonsei Univ, Coll Hlth Sci, Dept Biomed Lab Sci, Wonju 220710, South Korea

[4] Seoul Natl Univ, Biotechnol Incubating Ctr, ToolGen Inc, Seoul 305390, South Korea

[5] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA

[6] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA

[7] Genzyme Corp, Framingham, MA 01701 USA

[8] Konkuk Univ, Coll Vet Med, Seoul 143701, South Korea

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

基金：

新加坡国家研究基金会;

关键词：

PARKINSONS-DISEASE; MUTATIONS; CLEARANCE; DEMENTIA; NEURON; MULTICENTER; DEGRADATION; PATHOLOGY;

D O I：

10.1038/ncomms5755

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Deposition of alpha-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 alpha-synuclein aggregates is associated with the progression of PD, the mechanism by which alpha-synuclein aggregates spread remains undefined. Here, we show that alpha-synuclein aggregates are transmitted from cell to cell through a cycle involving uptake of external aggregates, co-aggregation with endogenous alpha-synuclein and exocytosis of the co-aggregates. Moreover, we find that glucocerebrosidase depletion, which has previously been strongly associated with PD and increased cognitive impairment, promotes propagation of alpha-synuclein aggregates. These studies define how alpha-synuclein aggregates spread among neuronal cells and may provide an explanation for how glucocerebrosidase mutations increase the risk of developing PD and other synucleinopathies.

引用

页数：11

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