Research Institute for Medicines and Pharmaceutical Sciences, University of Lisbon, Lisbon, Portugal.
Mol Neurobiol. 2012 Oct;46(2):316-31. doi: 10.1007/s12035-012-8289-2. Epub 2012 Jul 1.
Emerging evidence suggests that apoptosis regulators and executioners may control cell fate, without involving cell death per se. Indeed, several conserved elements of apoptosis are integral components of terminal differentiation, which must be restrictively activated to assure differentiation efficiency, and carefully regulated to avoid cell loss. A better understanding of the molecular mechanisms underlying key checkpoints responsible for neural differentiation, as an alternative to cell death will surely make stem cells more suitable for neuro-replacement therapies. In this review, we summarize recent studies on the mechanisms underlying the non-apoptotic function of p53, caspases, and Bcl-2 family members during neural differentiation. In addition, we discuss how apoptosis-regulatory proteins control the decision between differentiation, self-renewal, and cell death in neural stem cells, and how activity is restrained to prevent cell loss.
新出现的证据表明，凋亡调节因子和执行者可能控制细胞命运，而不涉及细胞死亡本身。事实上，凋亡的几个保守元素是终末分化的组成部分，必须严格激活以保证分化效率，并进行精细调节以避免细胞丢失。更好地理解负责神经分化的关键检查点的分子机制，作为细胞死亡的替代方案，肯定会使干细胞更适合神经替代疗法。在这篇综述中，我们总结了最近关于 p53、半胱天冬酶和 Bcl-2 家族成员在神经分化过程中发挥非凋亡功能的机制的研究。此外，我们还讨论了凋亡调节蛋白如何控制神经干细胞在分化、自我更新和细胞死亡之间的决策，以及如何限制活性以防止细胞丢失。
