Executioner Proteases

An increase in intracellular calcium is associated with necrotic-like cell death of neurons, but it is not clear how this signaling event ultimately kills cells. Syntichaki et al. report that calcium-regulated proteases are key to initiating the cell's demise. The study examined neuronal degeneration in touch receptor neurons of Caenorhabditis elegans expressing a hyperactive ion channel subunit of MEC-4. Such cells were previously observed to exhibit extensive intracellular degradation. Using genetic, pharmacological, and RNA interference approaches, the authors determined that both calpain and aspartyl proteases are required for this type of neurodegeneration. Deficiencies in these proteases partially protected against necrotic cell death, and overexpression caused spontaneous vacuolation of neurons. The authors propose that necrosis-like neurodegeneration involves deregulation of calcium-dependent proteolysis. P. Syntichaki, K. Xu, M. Driscoll, N. Tavernarakis, Specific aspartyl and calpain proteases are required for neurodegeneration in C. elegans . Nature 419 , 939-944 (2002). [Online Journal]