Background. Progressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by pure neurofibrillary tau pathology involving mainly basal ganglia and brain stem nuclei [1]. One of the kinases involved in tau phosphorylation is glycogen synthase 3 kinase (GSK3) [2]. In mammals GSK3 is present in two isoforms, a and b regulated by phosphorylation: phosphorylation of Ser9 in GSK3b or Ser21 in GSK3a leads to inactivation while phosphorylation of Tyr216 in GSK3b or Tyr279 in GSK3a leads to activation [3]. Objective. We analyzed the protein levels of GSK3a/b and of the phosphorylated forms GSK3b S9, GSK3b Y216, GSK3a Y279 in brain tissues of subjects with PSP. Methods. Twelve cases fulfilling the clinical and pathological NINCDS criteria for PSP (63-78 years old), and twelve age-matched controls (65-80 years old) were considered. Protein levels of all GSK3 isoforms were evaluated by western blot analysis on brain tissues homogenates. Results. The analysis failed to show significant differences among the three areas examined for all GSK3 isoforms in PSP in comparison to age-matched control cases. Conclusions. This negative result argues against the role of GSK3 in the pathogenesis of PSP. Thus, the hyperphosphorylation of tau occurring in PSP can be due to alterations of other enzymes, as the cyclin-dependent kinase 5, that we previously demonstrated to be elevated in PSP brain [4]. 1. Dickson DW. Neurodegenerative diseases with cytoskeletal pathology: a biochemical classification. Ann Neurol 1997; 42: 541-544. 2. Embi N, Rylatt DB, Cohen P. Glycogen synthase kinase-3 from rabbit skeletal muscle. Separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase Eur J Biochem. 1980 Jun;107(2):519-27. 3. Frame S, Cohen P. GSK3 takes centre stage more than 20 years after its discovery. Biochem J. 2001 Oct 1;359(Pt 1):1-16 4. Borghi R., Giliberto L., Assini A., Delacourte A., Perry G., Smith M. A., Strocchi P., Zaccheo D., Tabaton M.. Increase of CDK5 is related to neurofibrillary pathology in progressive supranuclear palsy. Neurology. 2002 Feb 26;58(4):589-92
Zaccheo D., Borghi R., Piccini A., Delacourte A., Strocchi P., Tabaton M. (2004). Protein levels of glycogen synthase 3 kinase are normal in progressive supranuclear palsy. s.l : s.n.
Protein levels of glycogen synthase 3 kinase are normal in progressive supranuclear palsy
STROCCHI, PAOLA;
2004
Abstract
Background. Progressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by pure neurofibrillary tau pathology involving mainly basal ganglia and brain stem nuclei [1]. One of the kinases involved in tau phosphorylation is glycogen synthase 3 kinase (GSK3) [2]. In mammals GSK3 is present in two isoforms, a and b regulated by phosphorylation: phosphorylation of Ser9 in GSK3b or Ser21 in GSK3a leads to inactivation while phosphorylation of Tyr216 in GSK3b or Tyr279 in GSK3a leads to activation [3]. Objective. We analyzed the protein levels of GSK3a/b and of the phosphorylated forms GSK3b S9, GSK3b Y216, GSK3a Y279 in brain tissues of subjects with PSP. Methods. Twelve cases fulfilling the clinical and pathological NINCDS criteria for PSP (63-78 years old), and twelve age-matched controls (65-80 years old) were considered. Protein levels of all GSK3 isoforms were evaluated by western blot analysis on brain tissues homogenates. Results. The analysis failed to show significant differences among the three areas examined for all GSK3 isoforms in PSP in comparison to age-matched control cases. Conclusions. This negative result argues against the role of GSK3 in the pathogenesis of PSP. Thus, the hyperphosphorylation of tau occurring in PSP can be due to alterations of other enzymes, as the cyclin-dependent kinase 5, that we previously demonstrated to be elevated in PSP brain [4]. 1. Dickson DW. Neurodegenerative diseases with cytoskeletal pathology: a biochemical classification. Ann Neurol 1997; 42: 541-544. 2. Embi N, Rylatt DB, Cohen P. Glycogen synthase kinase-3 from rabbit skeletal muscle. Separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase Eur J Biochem. 1980 Jun;107(2):519-27. 3. Frame S, Cohen P. GSK3 takes centre stage more than 20 years after its discovery. Biochem J. 2001 Oct 1;359(Pt 1):1-16 4. Borghi R., Giliberto L., Assini A., Delacourte A., Perry G., Smith M. A., Strocchi P., Zaccheo D., Tabaton M.. Increase of CDK5 is related to neurofibrillary pathology in progressive supranuclear palsy. Neurology. 2002 Feb 26;58(4):589-92I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
