Eckert 2008 J Mol Med: Difference between revisions
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| | |area=Respiration, Genetic knockout;overexpression | ||
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|discipline=Mitochondrial Physiology, Biomedicine, Environmental Physiology; Toxicology, Pharmacology; Biotechnology | |discipline=Mitochondrial Physiology, Biomedicine, Environmental Physiology; Toxicology, Pharmacology; Biotechnology | ||
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Revision as of 23:41, 11 August 2013
Eckert A, Hauptmann S, Scherping I, Meinhardt J, Rhein V, DrΓΆse S, Brandt U, FΓ€ndrich M, MΓΌller WE, GΓΆtz 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 Alzheimerβs disease (AD) and frontotemporal dementia (FTD). In addition to tau aggregates, the AD brain is further characterized by AΞ² peptide-containing plaques. When we addressed the role of AΞ², this indicated a synergistic action of tau and AΞ² pathology on the mitochondria. In the present study, we compared the toxicity of different AΞ²42 conformations in light of recent studies suggesting that oligomeric rather than fibrillar AΞ² might be the actual toxic species. Interestingly, both oligomeric and fibrillar, but not disaggregated (mainly monomeric) AΞ²42 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 AΞ²42. Finally, we found that aging specifically increased the sensitivity of mitochondria to oligomeric AΞ²42 damage indicating that oligomeric and fibrillar AΞ²42 are both toxic, but exert different degrees of toxicity. β’ Keywords: Alzheimerβs disease, Amyloid aggregates, Amyloid Ξ²-peptide, Amyloid toxicity, Fibrils, Frontotemporal dementia, Globulomer, Mitochondria, Oligomer, Protein aggregation, Respiration, Tau - Transgenic mice
β’ O2k-Network Lab: CH_Basel_Eckert A, DE_Frankfurt_Brandt U, DE Frankfurt Droese S
Labels: MiParea: Respiration, Genetic knockout;overexpression
Pathology: Neurodegenerative
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