Proteomic and functional analyses reveal a mitochondrial dysfunction in P301L tau transgenic mice

David, Della C., Hauptmann, Susanne, Scherping, Isabel, Schuessel, Katrin, Keil, Uta, Rizzu, Patrizia, Ravid, Rivka, Drose, Stefan, Brandt, Ulrich, Muller, Walter E., Eckert, Anne and Gotz, Juergen (2005) Proteomic and functional analyses reveal a mitochondrial dysfunction in P301L tau transgenic mice. Journal of Biological Chemistry, 280 25: 23802-23814. doi:10.1074/jbc.M500356200

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ324032_OA.pdf Full text (open access) application/pdf 611.26KB 0

Author David, Della C.
Hauptmann, Susanne
Scherping, Isabel
Schuessel, Katrin
Keil, Uta
Rizzu, Patrizia
Ravid, Rivka
Drose, Stefan
Brandt, Ulrich
Muller, Walter E.
Eckert, Anne
Gotz, Juergen
Title Proteomic and functional analyses reveal a mitochondrial dysfunction in P301L tau transgenic mice
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2005-06-24
Sub-type Article (original research)
DOI 10.1074/jbc.M500356200
Open Access Status File (Publisher version)
Volume 280
Issue 25
Start page 23802
End page 23814
Total pages 13
Place of publication Bethesda, MD, United States
Publisher American Society for Biochemistry and Molecular Biology
Language eng
Formatted abstract
Transgenic mice overexpressing the P301L mutant human tau protein exhibit an accumulation of hyperphosphorylated tau and develop neurofibrillary tangles. The consequences of tau pathology were investigated here by proteomics followed by functional analysis. Mainly metabolism-related proteins including mitochondrial respiratory chain complex components, antioxidant enzymes, and synaptic proteins were identified as modified in the proteome pattern of P301L tau mice. Significantly, the reduction in mitochondrial complex V levels in the P301L tau mice revealed using proteomics was also confirmed as decreased in human P301L FTDP-17 (frontotemporal dementia with parkinsonism linked to chromosome 17) brains. Functional analysis demonstrated a mitochondrial dysfunction in P301L tau mice together with reduced NADH-ubiquinone oxidoreductase activity and, with age, impaired mitochondrial respiration and ATP synthesis. Mitochondrial dysfunction was associated with higher levels of reactive oxygen species in aged transgenic mice. Increased tau pathology as in aged homozygous P301L tau mice revealed modified lipid peroxidation levels and the upregulation of antioxidant enzymes in response to oxidative stress. Furthermore, P301L tau mitochondria displayed increased vulnerability toward β-amyloid (Aβ) peptide insult, suggesting a synergistic action of tau and Aβ pathology on the mitochondria. Taken together, we conclude that tau pathology involves a mitochondrial and oxidative stress disorder possibly distinct from that caused by Aβ.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Centre for Ageing Dementia Research Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 187 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 200 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 26 Feb 2014, 18:24:32 EST by System User on behalf of Learning and Research Services (UQ Library)