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Recruitment of the mitochondrial-dependent apoptotic pathway in amyotrophic lateral sclerosis.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Guégan, Christelle Vila, Miquel Rosoklija, Gorazd B. Hays, Arthur P. Przedborski, Serge E. |
| Copyright Year | 2001 |
| Abstract | Molecular mechanisms of apoptosis may participate in motor neuron degeneration produced by mutant superoxide dismutase-1 (mSOD1), the only proven cause of amyotrophic lateral sclerosis (ALS). Consistent with this, here we show that the proapoptotic protein Bax translocates from the cytosol to the mitochondria, whereas cytochrome c translocates from the mitochondria to the cytosol in spinal cords of transgenic mSOD1 mice during the progression of the disease. Concomitantly, caspase-9 is activated in the spinal cord of transgenic mSOD1 mice. Only in end-stage transgenic mSOD1 mice is the downstream caspase-7 activated and the inhibitor of apoptosis, XIAP, cleaved. These results indicate a sequential recruitment of molecular elements of the mitochondrial-dependent apoptotic pathway in transgenic mSOD1 mice. We also provide immunohistochemical evidence that cytochrome c translocation occurs in the spinal cord of sporadic ALS patients. Collectively, these data suggest that the mitochondrial-dependent apoptotic pathway may contribute to the demise of motor neurons in ALS and that targeting key molecules of this cascade may prove to be neuroprotective. |
| Starting Page | 1356 |
| Ending Page | 1356 |
| Page Count | 1 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.jneurosci.org/content/jneuro/21/17/6569.full.pdf |
| Alternate Webpage(s) | http://www.jneurosci.org/content/21/17/6569.full.pdf |
| PubMed reference number | 11517246v1 |
| Volume Number | 21 |
| Issue Number | 17 |
| Journal | The Journal of neuroscience : the official journal of the Society for Neuroscience |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Amyotrophic Lateral Sclerosis Apoptosis Cascade Device Component Cleaved cell Cytoplasmic matrix Mitochondria Mitochondrial Inheritance Motor Neurons Motor neuron atrophy Nerve Degeneration Patients Spinal Cord Superoxides Tuberous Sclerosis XIAP gene caspase-7 caspase-9 downregulation of ferrisuperoxide dismutase activity superoxide dismutase 1 |
| Content Type | Text |
| Resource Type | Article |
