Die Rolle von Wnt-Proteinen in der neuronalen und dopaminergen Differenzierung adulter neuraler Stammzellen

Wnt蛋白在成体神经干细胞神经元和多巴胺能分化中的作用

• 批准号: 14843260
• 负责人: Professor Dr. Dieter Chichung Lie
• 金额: --
• 依托单位: Institut für Biochemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2005
• 资助国家: 德国
• 起止时间: 2004-12-31 至 2006-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/14843260?language=en
• 关键词: Die; Rolle; von; Wnt; Proteinen

Proliferating cells with the potential to differentiate into neurons and glia are present throughout the adult mammalian central nervous system (CNS). However, recruitment of these neural stem cells (NSCs) for repair of the diseased adult CNS is hampered by the current lack of knowledge about the molecular signaling pathways that control the differentiation of adult NSCs. My preliminary results suggest that Wnt-proteins play a major role in the regulation of neuronal and dopaminergic differentiation of adult NSCs. In this project, I propose to examine the role of Wnt-signaling in these processes on the cellular and molecular level in vitro and in vivo. Moreover, I propose to manipulate Wnt-signaling in the adult CNS with the goal to stimulate the neuronal and dopaminergic differentiation of endogenous NSCs in non-neurogenic regions commonly affected in neurodegenerative diseases. These studies will not only lead to a better understanding of the molecular signals controlling the behavior of adult NSCs but may ultimately have consequences for the design of novel therapeutic approaches in degenerative CNS disorders which aim at the recruitment of endogenous NSCs for replacement of dying neurons.

具有分化为神经元和胶质细胞潜能的增殖细胞存在于整个成年哺乳动物中枢神经系统（CNS）。然而，由于目前对控制成体神经干细胞分化的分子信号通路缺乏了解，这些神经干细胞（NSCs）用于修复病变的成体中枢神经系统的募集受到阻碍。我的初步结果表明，wnt蛋白在成人NSCs的神经元和多巴胺能分化调控中起主要作用。在这个项目中，我建议在体外和体内研究wnt信号在细胞和分子水平上在这些过程中的作用。此外，我建议在成人中枢神经系统中操纵wnt信号，目的是刺激神经退行性疾病中常见的非神经源性区域内源性NSCs的神经元和多巴胺能分化。这些研究不仅将导致更好地理解控制成人NSCs行为的分子信号，而且可能最终对设计针对退行性中枢神经系统疾病的新治疗方法产生影响，这些方法旨在招募内源性NSCs来替代死亡的神经元。