Castelo-Branco Gonçalo, Arenas Ernest
Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Stockholm, Sweden.
Neurodegener Dis. 2006;3(1-2):5-11. doi: 10.1159/000092086.
Dopaminergic (DA) neurons in the ventral midbrain (VM) are one of the major cell types lost in Parkinson's disease (PD). Proof of principle exists for cell replacement therapies for PD, but wider application is halted by the unavailability of abundant sources of DA neurons. Stem cells might constitute one of these sources. However, efficient protocols promoting their specific differentiation into a DA neuronal phenotype are required. In this review, we summarize the latest findings concerning the contribution of the Wnt family of glycolipoproteins in the development of VM DA neurons. Regulators of Wnt signaling are involved in several neurodevelopmental processes. Recent results indicate that Wnts are key regulators of proliferation and differentiation of DA precursors during VM neurogenesis and different Wnts have specific and unique activity profiles. Interestingly, chemical inhibitors of glycogen synthase kinase-3beta stabilize beta-catenin and increase DA differentiation in VM precursor cultures. We hereby propose that Wnts are likely to contribute in the future to improve stem/precursor cell replacement therapy approaches to PD.
中脑腹侧（VM）的多巴胺能（DA）神经元是帕金森病（PD）中主要丢失的细胞类型之一。PD细胞替代疗法的原理已得到证实，但由于缺乏丰富的DA神经元来源，其广泛应用受到阻碍。干细胞可能是这些来源之一。然而，需要有效的方案来促进它们向DA神经元表型的特异性分化。在这篇综述中，我们总结了关于糖脂蛋白Wnt家族在VM DA神经元发育中的作用的最新发现。Wnt信号的调节因子参与了多个神经发育过程。最近的结果表明，Wnts是VM神经发生过程中DA前体增殖和分化的关键调节因子，不同的Wnts具有特定且独特的活性谱。有趣的是，糖原合酶激酶-3β的化学抑制剂可稳定β-连环蛋白并增加VM前体细胞培养物中的DA分化。我们在此提出，Wnts未来可能有助于改进PD的干细胞/前体细胞替代治疗方法。
