Synphilin-1A: an aggregation-prone isoform of synphilin-1 that causes neuronal death and is present in aggregates from alpha-synucleinopathy patients.
Synphilin-1A: an aggregation-prone isoform of synphilin-1 that causes neuronal death and is present in aggregates from alpha-synucleinopathy patients.
复制标题
Synphilin-1A：synphilin-1 的一种易聚集亚型，可导致神经元死亡，存在于 α-突触核蛋白病患者的聚集体中。
DOI：
--
复制
发表时间：
2006
影响因子：
11.1
通讯作者：
S. Engelender
中科院分区：
文献类型：
--
作者：
A. Eyal;R. Szargel;Eyal Avraham;Esti Liani;J. Haskin;R. Rott;S. Engelender
α -突触核蛋白病是一组以含有α -突触核蛋白的细胞内包涵体存在为特征的神经系统疾病。我们之前证明突触蛋白-1与α -突触核蛋白相互作用，暗示在帕金森病中起作用。我们现在报告了synphilin-1A的鉴定和表征，synphilin-1的一种异构体，它具有增强的聚集特性并引起神经毒性。编码synphilin-1A和synphilin-1的两个转录本来自SNCAIP基因，但它们的外显子组织和用于翻译的初始阅读框不同。Synphilin-1A与α -突触核蛋白结合，诱导人胚胎肾293细胞、原代神经元培养细胞和人多巴胺能细胞形成细胞内聚集体。突触蛋白- 1a在神经元中的过度表达会导致显著的细胞毒性，而突触蛋白- 1a包涵体的形成会招募α -突触核蛋白，从而减弱这种毒性。Synphilin-1A存在于帕金森病和弥漫性路易体病患者的路易体中，并在弥漫性路易体病患者脑蛋白样品的洗涤剂不溶性部分中观察到。这些发现表明synphilin-1A可能有助于α -突触核蛋白病的神经元变性，也为包涵体在神经退行性疾病中的作用提供了重要的见解。
alpha-Synucleinopathies are a group of neurological disorders characterized by the presence of intracellular inclusion bodies containing alpha-synuclein. We previously demonstrated that synphilin-1 interacts with alpha-synuclein, implying a role in Parkinson's disease. We now report the identification and characterization of synphilin-1A, an isoform of synphilin-1, which has enhanced aggregatory properties and causes neurotoxicity. The two transcripts encoding synphilin-1A and synphilin-1 originate from the SNCAIP gene but differ in both their exon organization and initial reading frames used for translation. Synphilin-1A binds to alpha-synuclein and induces the formation of intracellular aggregates in human embryonic kidney 293 cells, primary neuronal cultures, and human dopaminergic cells. Overexpression of synphilin-1A in neurons results in striking cellular toxicity that is attenuated by the formation of synphilin-1A inclusions, which recruit alpha-synuclein. Synphilin-1A is present in Lewy bodies of patients with Parkinson's disease and Diffuse Lewy Body disease, and is observed in detergent-insoluble fractions of brain protein samples obtained from Diffuse Lewy Body disease patients. These findings suggest that synphilin-1A may contribute to neuronal degeneration in alpha-synucleinopathies and also provide important insights into the role of inclusion bodies in neurodegenerative disorders.
DOI：
10.1073/pnas.0401081101
发表时间：
2004-04-13
影响因子：
11.1
作者：
Liani, E;Eyal, A;Engelender, S
通讯作者：
Engelender, S
神经退行性疾病中 NACP/α-突触核蛋白的异常积累。
DOI：
--
发表时间：
1998
期刊：
The American journal of pathology
影响因子：
--
作者：
Takeda,A;Mallory,M;Sundsmo,M;Honer,W;Hansen,L;Masliah,E
通讯作者：
Masliah,E