Tang Bor Luen
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore.
NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117596, Singapore.
Cells. 2017 Aug 23;6(3):26. doi: 10.3390/cells6030026.
The proneural factor Achaete-scute complex-like 1 (Ascl1/Mash1) acts as a pioneering transcription factor that initializes neuronal reprogramming. It drives neural progenitors and non-neuronal cells to exit the cell cycle, and promotes neuronal differentiation by activating neuronal target genes, even those that are normally repressed. Importantly, force-expression of Ascl1 was shown to drive proliferative reactive astroglia formed during stroke and glioblastoma stem cells towards neuronal differentiation, and this could potentially diminish CNS damage resulting from their proliferation. As a pro-neural factor, Ascl1 also has the general effect of enhancing neurite growth by damaged or surviving neurons. Here, a hypothesis that brain pathologies associated with traumatic/ischemic injury and malignancy could be targeted with pro-neural factors that drives neuronal differentiation is formulated and explored. Although a good number of caveats exist, exogenous over-expression of Ascl1, alone or in combination with other factors, may be worth further consideration as a therapeutic approach in brain injury and cancer.
神经前体因子achaete - scute复合体样1（Ascl1/Mash1）作为一种先驱转录因子，启动神经元重编程。它促使神经祖细胞和非神经元细胞退出细胞周期，并通过激活神经元靶基因来促进神经元分化，甚至包括那些通常被抑制的基因。重要的是，Ascl1的强制表达已被证明能促使中风期间形成的增殖性反应性星形胶质细胞和胶质母细胞瘤干细胞向神经元分化，这可能会减少因其增殖导致的中枢神经系统损伤。作为一种神经前体因子，Ascl1还具有增强受损或存活神经元神经突生长的普遍作用。在此，我们提出并探讨了一个假说，即与创伤性/缺血性损伤和恶性肿瘤相关的脑部病变可以用驱动神经元分化的神经前体因子来靶向治疗。尽管存在诸多限制，但Ascl1单独或与其他因子联合的外源性过表达，作为脑损伤和癌症的一种治疗方法，可能值得进一步考虑。
