Neurodegenerative disorders such as Alzheimer's disease are associated with necrotic cell death, but the biochemical mechanisms behind these processes have been unclear. In October 31 Nature, Popi Syntichaki and colleagues at the Institute of Molecular Biology and Biotechnology, Heraklion, Crete, Greece, show that specific calpain proteases (intracellular papain-like cysteine proteases) and aspartyl proteases are required for neurodegeneration in Caenorhabditis elegans (Nature, 419:939-944, October 31, 2002).

Syntichaki et al. used C. elegans having different mutated aspartyl proteases, and treated them with calpain inhibitors. They observed that neuronal degeneration inflicted by various genetic lesions in C. elegans requires the activity of the calcium-regulated CLP-1 and TRA-3 calpain proteases and aspartyl proteases ASP-3 and ASP-4. In addition, they suggest that perturbation of intracellular concentrations of calcium may initiate neuronal degeneration by deregulating proteolysis.

"The identification of two specific classes of protease that are required for neurodegeneration in C. elegans...