Proteins in apoptotic pathways represent potential points of intervention in neurodegenerative disease. We identified several genes of interest that contain death domain such as CARD or Pyrin. We found that ASC and NALP10 were constitutively expressed in cerebellar neurons. More interestingly, expression levels of NALP1 and NALP5 were increased in two neuronal injury models. In addition, transient expression of recombinant NALP1 or NALP5 in neurons induced caspase-3 activation and apoptosis. These data suggest that NALP1 and NALP5 may regulate caspase activation and apoptosis in injured neurons, and thus represent novel molecular targets for therapeutic intervention in neurodegenerative disorders. (c) 2007 Elsevier Inc. All rights reserved.