Protein levels of glycogen synthase 3 kinase are normal in progressive supranuclear palsy

Protein levels of glycogen synthase 3 kinase are normal in progressive supranuclear palsy
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DOI:
10.1016/j.neulet.2004.05.014
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发表时间:
2004-08-05
影响因子:
2.5
通讯作者:
Tabaton, M
Tabaton, M
中科院分区:
医学4区
文献类型:
--
作者:
Borghi, R;Piccini, A;Tabaton, M

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进行性核上性麻痹(PSP)是一种神经退行性疾病,其特征在于主要涉及基底节和脑干核团的纯神经元性tau病变。参与tau磷酸化的激酶之一是糖原合成酶3激酶(GSK 3)。在哺乳动物中,GSK 3以两种亚型存在,α和β受磷酸化调节:GSK 3 β中Ser-9或GSK 3 α中Ser 21的磷酸化导致失活,而GSK 3 β中Tyr 216或GSK 3 α中Tyr 279的磷酸化导致活化。我们分析了PSP受试者脑组织中GSK 3 α/β和磷酸化形式GSK 3 β S-9、GSK 3 β Y-216、GSK 3 α Y-279的蛋白水平。与年龄匹配的对照病例相比,分析未能显示PSP中所有GSK 3亚型的显著差异。这一阴性结果反驳了GSK 3在PSP发病机制中的作用。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
Progressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by pure neurofibrillary tau pathology involving mainly basal ganglia and brain stem nuclei. One of the kinases involved in tau phosphorylation is glycogen synthase 3 kinase (GSK3). In mammals GSK3 is present in two isoforms, alpha and beta regulated by phosphorylation: phosphorylation of Ser-9 in GSK3beta or Ser21 in GSK3alpha leads to inactivation while phosphorylation of Tyr216 in GSK3beta or Tyr279 in GSK3alpha leads to activation. We analyzed the protein levels of GSK3alpha/beta and of the phosphorylated forms GSK3beta S-9, GSK3beta Y-216, GSK3alpha Y-279 in brain tissues of subjects with PSP. The analysis failed to show significant differences of all GSK3 isoforms in PSP in comparison to age-matched control cases. This negative result argues against the role of GSK3 in the pathogenesis of PSP. (C) 2004 Elsevier Ireland Ltd. All rights reserved.