Eckert 2008 J Mol Med
| Eckert A, Hauptmann S, Scherping I, Meinhardt J, Rhein V, Drรถse S, Brandt U, Fรคndrich M, Mรผller WE, Gรถtz J (2008) Oligomeric and fibrillar species of beta-amyloid (Abeta42) both impair mitochondrial function in P301L tau transgenic mice. J. Mol. Med. 86: 1255-1267. |
Eckert A, Hauptmann S, Scherping I, Meinhardt J, Rhein V, Droese S, Brandt U, Faendrich M, Mueller WE, Goetz J (2008) J. Mol. Med.
Abstract: We recently provided evidence for a mitochondrial dysfunction in P301L tau transgenic mice, a strain modeling the tau pathology of Alzheimerโs disease (AD) and frontotemporal dementia (FTD). In addition to tau aggregates, the AD brain is further characterized by Aฮฒ peptide-containing plaques. When we addressed the role of Aฮฒ, this indicated a synergistic action of tau and Aฮฒ pathology on the mitochondria. In the present study, we compared the toxicity of different Aฮฒ42 conformations in light of recent studies suggesting that oligomeric rather than fibrillar Aฮฒ might be the actual toxic species. Interestingly, both oligomeric and fibrillar, but not disaggregated (mainly monomeric) Aฮฒ42 caused a decreased mitochondrial membrane potential in cortical brain cells obtained from FTD P301L tau transgenic mice. This was not observed with cerebellar preparations indicating selective vulnerability of cortical neurons. Furthermore, we found reductions in state 3 respiration, the respiratory control ratio, and uncoupled respiration when incubating P301L tau mitochondria either with oligomeric or fibrillar preparations of Aฮฒ42. Finally, we found that aging specifically increased the sensitivity of mitochondria to oligomeric Aฮฒ42 damage indicating that oligomeric and fibrillar Aฮฒ42 are both toxic, but exert different degrees of toxicity. โข Keywords: Alzheimerโs disease, Amyloid aggregates, Amyloid ฮฒ-peptide, Amyloid toxicity, Fibrils, Frontotemporal dementia, Globulomer, Mitochondria, Oligomer, Protein aggregation, Respiration, Tau - Transgenic mice
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Stress:Genetic Defect; Knockdown; Overexpression"Genetic Defect; Knockdown; Overexpression" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property. Organism: Mouse Tissue;cell: Neurons; Brain"Neurons; Brain" is not in the list (Heart, Skeletal muscle, Nervous system, Liver, Kidney, Lung;gill, Islet cell;pancreas;thymus, Endothelial;epithelial;mesothelial cell, Blood cells, Fat, ...) of allowed values for the "Tissue and cell" property.
Regulation: Respiration; OXPHOS; ETS Capacity"Respiration; OXPHOS; ETS Capacity" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property., Coupling; Membrane Potential"Coupling; Membrane Potential" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property.
HRR: Oxygraph-2k, Method"Method" is not in the list (Oxygraph-2k, TIP2k, O2k-Fluorometer, pH, NO, TPP, Ca, O2k-Spectrophotometer, O2k-Manual, O2k-Protocol, ...) of allowed values for the "Instrument and method" property., Theory
