Neural stem cell differentiation is dependent upon endogenous caspase 3 activity.
Caspase proteases have become the focal point for the development and application of anti-apoptotic therapies in a variety of central nervous system diseases. However, this approach is based on the premise that caspase function is limited to invoking cell death signals. Here, we show that caspase-3 activity is elevated in nonapoptotic differentiating neuronal cell populations. Moreover, peptide inhibition of protease activity effectively inhibits the differentiation process in a cultured neurosphere model. These results implicate caspase-3 activation as a conserved feature of neuronal differentiation and suggest that targeted inhibition of this protease in neural cell populations may have unintended consequences.
Fernando
Pasan
P
Ottawa Health Research Institute, Molecular Medicine Program, Ottawa, Ontario, Canada.
Brunette
Steve
S
Megeney
Lynn A
LA
D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000196:embryology*; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis* / Q000378:metabolism; D002454:Cell Differentiation; D004789:Enzyme Activation; D005434:Flow Cytometry; D015151:Immunoblotting; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D051379:Mice; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D013234:Stem Cells / Q000166:cytology*; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D010455:Peptides; D048051:p38 Mitogen-Activated Protein Kinases; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases