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Cytochrome C and caspase-9 expression in Huntington's disease.

Authors: Kiechle, Tamara  Dedeoglu, Alpaslan  Kubilus, James  Kowall, Neil W  Beal, M Flint  Friedlander, Robert M  Hersch, Steven M  Ferrante, Robert J 
Citation: Kiechle T, etal., Neuromolecular Med. 2002;1(3):183-95.
Pubmed: (View Article at PubMed) PMID:12095160
DOI: Full-text: DOI:10.1385/NMM:1:3:183

There is increasing evidence implicating apoptosis-mediated cell death in the pathogenesis of neurodegenerative diseases. One important event in the apoptotic cascade is the release of cytochrome c by mitochondria into the cytoplasm, activating caspase-9, leading to the subsequent activation of downstream executioner caspases. In the present study, we examined the distribution of cytochrome c and caspase-9 in Huntington's disease (HD) patients and in a transgenic model of HD (R6/2 line). Neuronal cytochrome c immunoreactivity increased with neuropathological severity in HD patients. Concomitant with this finding, Western-blot analysis showed a shift in the distribution of cytochrome c from the mitochondrial to the cytosolic fraction with incremental cytosolic expression associated with greater striatal degeneration. Active caspase-9 immunoreactivity was present in both HD striatal neurons and in Western blots of severe-grade specimens. Similar findings were observed in the R6/2 mice. There was a temporal increase in expression and shift of cytochrome c from the mitochondrial to the cytosolic fraction from 4-13 wk of age. Activated caspase-9 and caspase 3 activities were present only at endstage disease. Although the present results provide evidence that key components of the intrinsic mitochondrial apoptotic pathway are activated in both HD patients and a transgene murine model of HD, these phenomena are prominent in only severe neuropathological grades in HD patients and HD mice, suggesting that apoptosis may play a greater role in neuronal death at endstage disease.

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RGD Object Information
RGD ID: 13432083
Created: 2017-09-19
Species: All species
Last Modified: 2017-09-19
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.