Borghi Roberta, Piccini Alessandra, Delacourte Andrè, Strocchi Paola, Zaccheo Damiano, Tabaton Massimo
Department of Neurosciences, Ophthalmology and Genetic, University of Genova, Via De Toni, 5, 16132 Genova, Italy.
Neurosci Lett. 2004 Aug 5;366(1):67-70. doi: 10.1016/j.neulet.2004.05.014.
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 Ser9 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.
进行性核上性麻痹（PSP）是一种神经退行性疾病，其特征为单纯的神经原纤维缠结病理改变，主要累及基底神经节和脑干核团。参与tau蛋白磷酸化的激酶之一是糖原合酶3激酶（GSK3）。在哺乳动物中，GSK3有两种亚型，即α和β，其活性受磷酸化调节：GSK3β的Ser9或GSK3α的Ser21磷酸化会导致其失活，而GSK3β的Tyr216或GSK3α的Tyr279磷酸化会导致其激活。我们分析了PSP患者脑组织中GSK3α/β以及磷酸化形式GSK3β S(9)、GSK3β Y(216)、GSK3α 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患者所有GSK3亚型存在显著差异。这一阴性结果反驳了GSK3在PSP发病机制中的作用。
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