Cytoplasmic aggregates of dynactin in iPSC-derived tyrosine hydroxylase-positive neurons from a patient with Perry syndrome
Cytoplasmic aggregates of dynactin in iPSC-derived tyrosine hydroxylase-positive neurons from a patient with Perry syndrome
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DOI：
10.1016/j.parkreldis.2016.06.007
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发表时间：
2016-09-01
影响因子：
4.1
通讯作者：
Inoue, Haruhisa
中科院分区：
文献类型：
--
作者：
Mishima, Takayasu;Ishikawa, Taizo;Inoue, Haruhisa
背景：佩里综合征是一种罕见的常染色体显性遗传疾病，临床特征为帕金森病伴抑郁/冷漠、体重减轻和中枢性通气不足。据报道，DCTN1 基因有 8 种突变。由于详细的发病机制尚不清楚，因此需要一种新的疾病模型。方法：为了开发一种新的模型，我们从 DCTN1 具有 F52L 突变的佩里综合征患者中产生了诱导多能干细胞 (iPSC)，并描述了临床和神经影像学研究。我们将 iPSC 分化为酪氨酸羟化酶 (TH) 阳性神经元。对对照和突变体进行免疫细胞化学分析。结果：患者表现出左旋多巴反应性帕金森症。多巴胺转运蛋白单光子发射断层扫描显示纹状体的摄取明显减少，间碘苄胍心脏闪烁扫描也显示摄取减少。 Perry综合征TH阳性神经元在细胞质中显示出动力蛋白聚集体。结论：来自Perry综合征iPSC的TH阳性神经元再现了Perry综合征疾病表型的一个方面。 (C) 2016 Elsevier Ltd. 保留所有权利。
Background: Perry syndrome is a rare autosomal dominant disorder clinically characterized by parkinsonism with depression/apathy, weight loss, and central hypoventilation. Eight mutations in DCTN1 gene have been reported. A novel disease model is required because the detailed pathogenesis remains unclear.Methods: To develop a novel model, we generated induced pluripotent stem cells (iPSCs) from a Perry syndrome patient with F52L mutation in DCTN1, and describe clinical and neuroimaging investigations. We differentiated iPSCs into tyrosine hydroxylase (TH)-positive neurons. Immunocytochemistry analyses of control and mutant were performed.Results: The patient displayed levodopa responsive parkinsonism. Dopamine transporter single photon emission tomography showed markedly decreased uptake in the striatum, and metaiodobenzylguanidine cardiac scintigraphy also showed decreased uptake. Perry syndrome TH-positive neurons showed dynactin aggregates in cytoplasm.Conclusions: TH-positive neurons from Perry syndrome iPSCs recapitulated an aspect of the disease phenotype of Perry syndrome. (C) 2016 Elsevier Ltd. All rights reserved.