Modelling Alzheimer-specific abnormal Tau phosphorylation independently of GSK3beta and PKA kinase activities.
In Alzheimer's disease, neurofibrillary degeneration results from the aggregation of abnormally phosphorylated Tau proteins into paired helical filaments. These Tau variants displayed specific epitopes that are immunoreactive with anti-phospho-Tau antibodies such as AT100. As shown in in vitro experiments, glycogen synthase kinase 3 beta (GSK3beta) and protein kinase A (PKA) may be key kinases in these phosphorylation events. In the present study, Tau was microinjected into Xenopus oocytes. Surprisingly, in this system, AT100 was generated without any GSK3beta and PKA contribution during the progesterone or insulin-induced maturation process. Our results demonstrate that a non-modified physiological process in a cell model can generate the most specific Alzheimer epitope of Tau pathology.
Delobel
P
P
INSERM U422, IMPRT, Institut de Médecine Prédictive et Recherche Thérapeutique, Place de Verdun, 59045, Lille, France.
Flament
S
S
Hamdane
M
M
Delacourte
A
A
Vilain
J P
JP
Buée
L
L
D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D006801:Humans; D066298:In Vitro Techniques; D018021:Lithium Chloride / Q000494:pharmacology; D008954:Models, Biological; D009865:Oocytes / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D014981:Xenopus; D016875:tau Proteins / Q000737:chemistry* / Q000378:metabolism*
D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D016875:tau Proteins; D038341:Glycogen Synthase Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride