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.

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.

Unlike rat neurons, mice sympathetic neurons were not protected by CsA. Neuron...