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Neurodegenerative disease

Synergistic destruction

Nature Reviews Neuroscience volume 11, page 4 (2010)Cite this article

The authors used quantitative proteomic analysis of the forebrains of 10-month-old wild-type mice, single-transgenic pR5 mice (carrying a neurofibrillary-tangle-forming P301L tau mutation), double-transgenic APP–PS2 mice (which carry mutations in both amyloid precursor protein and presenilin 2 and develop Aβ plaques) and tripleAD (pR5–APP–PS2) mice. They identified 24 proteins that were strongly deregulated in the tripleAD mice. One-third of these were mitochondrial proteins related to complexes I and IV of the OXPHOS.

In accordance with the proteomic findings, the efficiency of the OXPHOS was reduced in cerebral mitochondria isolated from APP–PS2 mice and — to a higher degree — tripleAD mice at 12 months. The mitochondrial function of pR5 mice was not affected at this age, in accordance with previous studies.

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References

ORIGINAL RESEARCH PAPER

  1. Rhein, V. et al. Amyloid-β and tau synergistically impair the oxidative phosphorylation system in triple transgenic Alzheimer's disease mice. Proc. Natl Acad. Sci. USA 6 Nov 2009 (doi:10.1073/pnas.0905529106)

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FURTHER READING

  1. Bayés, A. & Grant, S. G. N. Neuroproteomics: understanding the molecular organization and complexity of the brain. Nature Rev. Neurosci. 10, 635–646 (2009)

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Authors
  1. Claudia Wiedemann
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Wiedemann, C. Synergistic destruction. Nat Rev Neurosci 11, 4 (2010). https://doi.org/10.1038/nrn2777

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