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
โข O2k-Network Lab: CH_Basel_Eckert A, DE_Frankfurt_Brandt U, DE Frankfurt Droese S
Labels:
Stress:Mitochondrial Disease; Degenerative Disease and Defect"Mitochondrial Disease; Degenerative Disease and Defect" 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., 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: Nervous system Preparation: Isolated Mitochondria"Isolated Mitochondria" is not in the list (Intact organism, Intact organ, Permeabilized cells, Permeabilized tissue, Homogenate, Isolated mitochondria, SMP, Chloroplasts, Enzyme, Oxidase;biochemical oxidation, ...) of allowed values for the "Preparation" property.
HRR: Oxygraph-2k
