title: Tenascin-C deficiency ameliorates Alzheimer's disease-related pathology in mice.
abstract: Alzheimer's disease (AD) is a neurodegenerative disease characterized by deposits of amyloid β peptide (Aβ) and microglia-driven inflammatory activation. Tenascin-C (tnc) is an extracellular matrix protein that is upregulated in inflammation and induces further inflammatory responses. We hypothesized that tnc contributes to the inflammatory pathology in AD. Using real-time polymerase chain reaction, we observed that tnc gene transcription was upregulated in cultured microglia after Aβ challenge and in the brain of an AD mouse model that overexpresses mutated amyloid precursor protein (APP) in neural cells. By cross-breeding APP-transgenic mice and tenascin-C-deficient mice, we demonstrated using real-time polymerase chain reaction, Western blot analysis, enzyme-linked immunosorbent assay, and immunohistochemistry that tnc deficiency reduces pro- but enhances anti-inflammatory activation in the mutated APP-transgenic mouse brain, associated with a reduced cerebral Aβ load and higher levels of the postsynaptic density protein 95. Thus, our study indicates that functional inhibition of tnc exerts beneficial effects on AD pathogenesis, suggesting a potential for tnc as a new therapeutic target in AD.
authors.affiliation: Department of Neurology, University of the Saarland, Homburg/Saar, Germany.
authors.forename: Kan
authors.initials: K
authors.lastname: Xie
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Wenlin
authors.initials: W
authors.lastname: Hao
authors.forename: Silke
authors.initials: S
authors.lastname: Walter
authors.forename: Botond
authors.initials: B
authors.lastname: Penke
authors.forename: Tobias
authors.initials: T
authors.lastname: Hartmann
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
authors.forename: Klaus
authors.initials: K
authors.lastname: Fassbender
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D058990:Molecular Targeted Therapy; D019063:Tenascin / Q000172:deficiency* / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D016229:Amyloid beta-Peptides; D019063:Tenascin
keywords: Alzheimer's disease; Aβ; Inflammation; Neurodegeneration; Tenascin-C