References
Query Results -- Details
MGI Accession ID: MGI:2149267
J Number: J:71177
Other Accession IDs:
Title: Recruitment of the mitochondrial-dependent apoptotic pathway in amyotrophic lateral sclerosis.
Authors: Guegan C; Vila M; Rosoklija G; Hays AP; Przedborski S
Journal: J Neurosci
Volume: 21
Issue: 17
Date: 2001 Sep 1
Year: 2001
Pages: 6569-76
Review Status: Peer Reviewed
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.
Additional Information:
