标题: Blocking caspase-independent death [打印本页] 作者: 杨柳 时间: 2009-3-6 00:16 标题: Blocking caspase-independent death
Apoptotic cell death is executed by the caspase family of cysteine proteases. Apoptosis of injured neuronal cells can be inhibited by blocking caspases, but these cells still die eventually, via a second, nonapoptotic, mechanism that is not well understood. On page 771, Chang and Johnson demonstrate that this process can be prevented by blocking loss of mitochondrial membrane potential.3 j5 e+ r, [) X# E
7 w0 c7 p+ T% S$ ` U0 {Using growth factor–deprived sympathetic neurons from rats, the authors found that cyclosporin A (CsA) provided protection to rat neurons from caspase- independent cell death. The drug probably acts by blocking the opening of the mitochondrial permeability transition pore (PTP), and thus preventing depolarization of the mitochondrial membrane. When caspases were active, CsA had no effect, suggesting that PTP opening is not critical during apoptosis. " ^% U: h" c D* Y# }* w# v1 w' Y. d2 P; y
Unlike rat neurons, mice sympathetic neurons were not protected by CsA. Neuron size may account for this difference, as smaller cells may be unable to survive until CsA arrives and mitochondria can reestablish their ion gradient. Johnson is optimistic that combinations of caspase inhibitors and CsA will have neuroprotective benefits in patients who have suffered a heart attack or stroke, although CsA may not be able to be given at a high enough does to completely block PTP.(More neurons survive nonapoptotic death )作者: 舒思 时间: 2015-6-1 13:26