title: Chronic lithium treatment decreases mutant tau protein aggregation in a transgenic mouse model.
abstract: Tau protein hyperphosphorylation and aggregation into neurofibrillary tangles are characteristic features of several neurodegenerative disorders referred to as tauopathies. Among them, frontotemporal dementia and Parkinsonism linked to chromosome 17 may be caused by dominant missense mutations in the tau gene. Transgenic mice expressing mutant tau serve as valid model systems to study the ethiopathogenesis of these diseases and assay possible therapeutic interventions. Here we report that chronic lithium treatment of a transgenic mouse strain expressing human tau with three missense mutations results in decreased glycogen synthase kinase-3-dependent-tau phosphorylation and a reduction of filamentous aggregates. These data indicate that lithium, presumably acting through the inhibition of glycogen synthase kinase 3, may be useful to curb neurodegeneration in tauopathies.
authors: Centro de Biología Molecular Severo Ochoa, (CSIC/UAM) Facultad de Ciencias, Universidad Autónoma de Madrid, Madrid 28049, Spain.
authors: Mar
authors: M
authors: Pérez
authors: Félix
authors: F
authors: Hernández
authors: Filip
authors: F
authors: Lim
authors: Javier
authors: J
authors: Díaz-Nido
authors: Jesús
authors: J
authors: Avila
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D003704:Dementia / Q000235:genetics* / Q000473:pathology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors; D006801:Humans; D007150:Immunohistochemistry; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000235:genetics; D016253:Microscopy, Immunoelectron; D020125:Mutation, Missense; D016874:Neurofibrillary Tangles / Q000187:drug effects* / Q000473:pathology; D010375:Pedigree; D024801:Tauopathies / Q000235:genetics* / Q000473:pathology; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D016875:tau Proteins; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride