title: Mitochondrial dysfunction induced by disease relevant AbetaPP and tau protein mutations.
abstract: Alzheimer's disease is characterized by two major pathological hallmarks: extracellular plaques consisting of amyloid beta peptide and neurofibrillary tangles composed of hyperphosphorylated tau protein. Mutations in the amyloid beta-protein precursor (AbetaPP) have been linked to familial Alzheimer's disease. They are leading to increased amyloid beta production. Mutations in the tau gene have not been described in AD, but are leading to formation of neurofibrillary tangles very similar to filaments in AD brains, and are therefore of increasing relevance in AD research. Interestingly, our data indicate that mutations in AbetaPP gene and mutations in tau gene induce mitochondrial dysfunction and oxidative stress in cell culture models and transgenic mice. Thus, both Alzheimer relevant protein alterations seem to have synergistic actions probably at the level of mitochondria leading to synaptic dysfunction and apoptotic cell death.
authors.affiliation: Department of Pharmacology, Biocenter, University of Frankfurt, 60439 Frankfurt, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Keil
authors.forename: Susanne
authors.initials: S
authors.lastname: Hauptmann
authors.forename: Astrid
authors.initials: A
authors.lastname: Bonert
authors.forename: Isabel
authors.initials: I
authors.lastname: Scherping
authors.forename: Anne
authors.initials: A
authors.lastname: Eckert
authors.forename: Walter E
authors.initials: WE
authors.lastname: Müller
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001792:Blood Platelets / Q000502:physiology; D005110:Extracellular Space / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000502:physiology; D028361:Mitochondrial Diseases / Q000235:genetics*; D009154:Mutation / Q000502:physiology*; D010766:Phosphorylation; D014162:Transfection; D016875:tau Proteins / Q000235:genetics*
chemical_list: D016564:Amyloid beta-Protein Precursor; D016875:tau Proteins