Neural stem cell differentiation is dependent upon endogenous caspase-3 activity
Neural stem cell differentiation is dependent upon endogenous caspase-3 activity
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DOI：
10.1096/fj.04-2981fje
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发表时间：
2005-08-01
期刊：
影响因子：
4.8
通讯作者：
Megeney, LA
中科院分区：
文献类型：
--
作者：
Fernando, P;Brunette, S;Megeney, LA
半胱天冬酶已成为开发和应用抗凋亡疗法在各种中枢神经系统疾病的焦点。然而，这种方法是基于这样的前提，即半胱天冬酶功能仅限于调用细胞死亡信号。在这里，我们表明，caspase-3活性升高，在非凋亡分化的神经元细胞群。此外，蛋白酶活性的肽抑制有效地抑制了培养的神经球模型中的分化过程。这些结果暗示半胱天冬酶-3激活作为神经元分化的保守特征，并表明在神经细胞群中靶向抑制这种蛋白酶可能具有意想不到的后果。
Caspase proteases have become the focal point for the development and application of antiapoptotic 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.