近日，复旦大学医学神经生物学国家重点实验室、脑科学研究院教授赵冰樵带领研究团队首次发现，脑内一种名叫“caspase-3”的分子，一旦被激活，不仅在人的脑卒中发生初期起“细胞杀手”作用，而且在脑卒中的恢复期继续起破坏作用；研究团队还发现，药物可以抑制caspase-3的破坏作用，从而促进脑卒中后神经干细胞的再生。目前该成果已刊登在最新一期著名学术期刊《干细胞》上。
脑卒中造成的神经功能障碍，临床上至今尚无有效治疗手段。脑损伤后，新生神经干细胞的存活能力和形成成熟神经细胞的能力都非常有限。因此，脑卒中后神经干细胞再生和分化机制研究，以及如何促进神经元的有效新生，如何重塑脑中风后受损的神经功能，一直是困扰脑中风研究领域的重大瓶颈。
赵冰樵团队研究发现，caspase-3是脑内神经干细胞再生的重要抑制分子，也是一种关键的导致正常细胞死亡的执行因子。团队还研究发现，脑卒中虽然引起caspase-3在小鼠脑内神经干细胞中大量聚集，即便采用多种实验手段，这些caspase-3也并不执行让细胞凋亡的功能。他们进一步研究证实，使用药物可以抑制caspase-3的活性，从而促进脑卒中后神经干细胞的再生，并可加快新生神经干细胞向成熟神经细胞即神经元转化，协助脑损伤后的功能修复。
以往的研究仅证明抑制caspase-3的活性后，对急性脑卒中具有保护作用，但赵冰樵团队的研究结果进一步证明caspase-3在脑卒中后继续有破坏作用。该成果不但对临床上如何促进脑卒中后的神经再生，而且对开发既保护脑损伤又促进脑损伤后功能重塑、找到新型治疗药物新靶点具有重要意义。（生物谷 Bioon.com）
生物谷推荐的英文摘要
Stem Cell DOI: 10.1002/stem.1503
Caspase-3 Modulates Regenerative Response after Stroke
Wenying Fan1,*, Yiqin Dai1, Haochen Xu1, Ximin Zhu1, Ping Cai1, Lixiang Wang1, Chungang Sun1, Changlong Hu1,2, Ping Zheng1, Bing-Qiao Zhao1,*
Stroke is a leading cause of long-lasting disability in humans. However, currently there are still no effective therapies available for promoting stroke recovery. Recent studies have shown that the adult brain has the capacity to regenerate neurons after stroke. Although this neurogenic response may be functionally important for brain repair after injury, the mechanisms underlying stroke-induced neurogenesis are not known. Caspase-3 is a major executioner and has been identified as a key mediator of neuronal death in the acute stage of stroke. Recently however, accumulating data indicate that caspase-3 also participate in various biological processes that do not cause cell death. Here, we show that cleaved caspase-3 was increased in newborn neuronal precursor cells (NPCs) in the subventricular zone (SVZ) and the dentate gyrus (DG) during the period of stroke recovery, with no evidence of apoptosis. We observed that cleaved caspase-3 was expressed by NPCs and limited its self-renewal without triggering apoptosis in cultured NPCs from the SVZ of ischemic mice. Moreover, we revealed that caspase-3 negatively regulated the proliferation of NPCs through reducing the phosphorylation of Akt. Importantly, we demonstrated that peptide inhibition of caspase-3 activity significantly promoted the proliferation and migration of SVZ NPCs, and resulted in a significant increase in subsequent neuronal regeneration and functional recovery after stroke. Together, our data identify a previously unknown caspase-3-dependent mechanism that constrains stroke-induced endogenous neurogenesis and should revitalize interest in targeting caspase-3 for treatment of stroke.
