Function of Wnts in dopaminergic neuron development
Function of Wnts in dopaminergic neuron development
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DOI：
10.1159/000092086
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发表时间：
2006-01-01
影响因子：
3
通讯作者：
Arenas, Ernest
中科院分区：
文献类型：
--
作者：
Castelo-Branco, Goncalo;Arenas, Ernest
多巴胺能（DA）神经元是帕金森病（PD）中缺失的主要细胞类型之一。PD的细胞替代疗法的原理证明已经存在，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，促进其特异性分化为DA神经元表型的有效方案是必需的。在这篇综述中，我们总结了关于Writ家族糖糖蛋白在VM DA神经元发育中的贡献的最新发现。Wnt信号的调节因子参与了几个神经发育过程。最近的研究结果表明，wnt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wnt具有特异性和独特的活性谱。有趣的是，糖原合成酶激酶-3 β的化学抑制剂稳定了β -连环蛋白，并增加了VM前体培养中的DA分化。我们在此提出，Writs在未来可能有助于改善PD的干细胞/前体细胞替代治疗方法。
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 Writ family of glycolipoproteins in the development of VM DA neurons. Regulators of Wnt signaling are involved in several neurodevelopmental processes. Recent results indicate that Writs 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-3 beta stabilize beta-catenin and increase DA differentiation in VM precursor cultures. We hereby propose that Writs are likely to contribute in the future to improve stem/precursor cell replacement therapy approaches to PD.