Defined α-synuclein prion-like molecular assemblies spreading in cell culture.
Defined α-synuclein prion-like molecular assemblies spreading in cell culture.
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DOI：
10.1186/1471-2202-15-69
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发表时间：
2014-06-04
期刊：
影响因子：
2.4
通讯作者：
Legname G
中科院分区：
文献类型：
--
作者：
Aulić S;Le TT;Moda F;Abounit S;Corvaglia S;Casalis L;Gustincich S;Zurzolo C;Tagliavini F;Legname G
α-突触核蛋白（α-syn）在突触核蛋白病（synucleinopathies）的发病机制中起核心作用，突触核蛋白病是一组神经退行性疾病，包括帕金森病、路易体痴呆和多系统萎缩。来自细胞培养和小鼠实验的几个发现表明细胞间α-syn转移。通过用于获得合成哺乳动物朊病毒的方法，我们测试了重组人α-syn淀粉样蛋白是否可以促进体外神经元细胞系中朊病毒样积累。单次暴露于人α-syn的淀粉样纤维足以诱导人神经母细胞瘤SH-SY 5 Y细胞中内源性α-syn的聚集。值得注意的是，内源性野生型α-syn足以形成这些聚集体，并且不需要蛋白质的过表达。我们的研究结果提供了令人信服的证据，即内源性α-syn可以在单次暴露于外源性α-syn短淀粉样纤维后在细胞培养物中积累。重要的是，使用α-syn短淀粉样蛋白原纤维作为种子，内源性α-syn聚集并在细胞培养物中经过几代积累，为潜在的治疗性筛选致病性α-syn聚集体提供了极好的工具。
α-Synuclein (α-syn) plays a central role in the pathogenesis of synucleinopathies, a group of neurodegenerative disorders that includes Parkinson disease, dementia with Lewy bodies and multiple system atrophy. Several findings from cell culture and mouse experiments suggest intercellular α-syn transfer. Through a methodology used to obtain synthetic mammalian prions, we tested whether recombinant human α-syn amyloids can promote prion-like accumulation in neuronal cell lines in vitro. A single exposure to amyloid fibrils of human α-syn was sufficient to induce aggregation of endogenous α-syn in human neuroblastoma SH-SY5Y cells. Remarkably, endogenous wild-type α-syn was sufficient for the formation of these aggregates, and overexpression of the protein was not required. Our results provide compelling evidence that endogenous α-syn can accumulate in cell culture after a single exposure to exogenous α-syn short amyloid fibrils. Importantly, using α-syn short amyloid fibrils as seed, endogenous α-syn aggregates and accumulates over several passages in cell culture, providing an excellent tool for potential therapeutic screening of pathogenic α-syn aggregates.
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DOI：
10.1523/jneurosci.3088-11.2011
发表时间：
2011-10-12
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Langer F;Eisele YS;Fritschi SK;Staufenbiel M;Walker LC;Jucker M
通讯作者：
Jucker M
影响因子：
15.1
作者：
Sacino AN;Thomas MA;Ceballos-Diaz C;Cruz PE;Rosario AM;Lewis J;Giasson BI;Golde TE
通讯作者：
Golde TE
影响因子：
64.8
作者：
Silveira, JR;Raymond, GJ;Caughey, B
通讯作者：
Caughey, B
影响因子：
56.9
作者：
Meyer-Luehmann, Melanie;Coomaraswamy, Janaky;Jucker, Mathias
通讯作者：
Jucker, Mathias
影响因子：
3.3
作者：
Schell, H.;Hasegawa, T.;Kahle, P. J.
通讯作者：
Kahle, P. J.