title: Astrocytic neuroprotection through induction of cytoprotective molecules; a proteomic analysis of mutant P301S tau-transgenic mouse.
abstract: Hyperphosphorylated tau protein constitutes a significant portion of intracellular inclusions in some neurodegenerative diseases. In addition, mutations in tau protein cause familial forms of frontotemporal dementia (FTD), indicating that dysfunction of tau protein is responsible for neurodegeneration and dementia. P301S tau-transgenic (Tg) mouse expressing human mutant tau in neurons exhibits similar features of human tauopathies including neuronal degeneration and filament accumulation consisted of hyperphosphorylated tau protein. In the present study, we attempted to characterize protein expression profiles in P301S tau-Tg mouse by using two-dimensional differential in-gel electrophoresis (2D-DIGE) coupled by peptide mass fingerprinting (PMF). As a result, we identified four upregulated proteins; heat shock protein 27 (Hsp27), peroxiredoxin 6 (Prdx6), apolipoprotein E (ApoE), and latexin (LTXN), all of which may function as a neuroprotective mechanism against tau toxicity. In immunohistochemistry, these four proteins were increased invariably in astrocytes, and these astrocytes infiltrated the area in which there are numerous accumulations of hyperphosphorylated tau and neuronal loss. Therefore, these results may indicate that astrocytes provide a neuroprotective mechanism against tau toxicity.
authors.affiliation: Department of Neurology, Mie University Graduate School of Medicine, Tsu 514-8507, Japan. ken-yata@mbk.nifty.com
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Yata
authors.forename: Shinji
authors.initials: S
authors.lastname: Oikawa
authors.forename: Ryogen
authors.initials: R
authors.lastname: Sasaki
authors.forename: Akihiro
authors.initials: A
authors.lastname: Shindo
authors.forename: Rong
authors.initials: R
authors.lastname: Yang
authors.forename: Mariko
authors.initials: M
authors.lastname: Murata
authors.forename: Kenji
authors.initials: K
authors.lastname: Kanamaru
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Tomimoto
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death; D019610:Cytoprotection / Q000502:physiology*; D004195:Disease Models, Animal; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D054465:Peroxiredoxin VI / Q000378:metabolism; D010766:Phosphorylation; D024801:Tauopathies / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000941:Antigens; D001057:Apolipoproteins E; D055551:HSP27 Heat-Shock Proteins; C086812:Lxn protein, rat; D016875:tau Proteins; D054465:Peroxiredoxin VI; C515983:Prdx6 protein, mouse