hUC-MSCs抑制神经元核内包涵体形成治疗SCA3型的研究

项目名称： hUC-MSCs抑制神经元核内包涵体形成治疗SCA3型的研究

项目编号： No.81200876

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 刘卓

作者单位： 南京大学

项目金额： 24万元

中文摘要： 脊髓小脑性共济失调3型(SCA3)是我国常见的遗传性神经系统变性疾病，目前尚无有效的预防和治疗手段。文献和我们前期研究提示人脐带间充质干细胞（hUC-MSCs）是一种理想的治疗SCA的种子细胞。为了进一步探讨hUC-MSCs在SCA3这类多聚谷氨酰胺疾病中具有的治疗作用及其可能机制，本课题将从整体到分子水平，以B6.SCA3-YAC-84Q转基因小鼠为SCA3动物模型，研究：1、hUC-MSCs是否能够抑制神经元核内包涵体形成，避免神经元损伤，从而改善共济失调症状？2、hUC-MSCs是否通过旁分泌作用对SCA3发挥神经保护功能?3、hUC-MSCs上述神经保护作用的相关分子机制。我们期望通过阐明hUC-MSCs对SCA3型治疗作用可能的分子机制，为干细胞临床应用治疗此类多聚谷氨酰胺疾病奠定坚实的基础。

中文关键词： 脊髓小脑共济失调3型；人脐带间充质干细胞；核内包涵体；热休克蛋白70；细胞凋亡

英文摘要： Spinocerebellar ataxia type 3 (SCA3) is the most uinversal type of SCA which is a heterogeneous group of hereditary neurodegenerative disease in our country and there is no effective treatment.The documents and our earlier research have shown that human umbilical cord mesenchymal stem cell (hUC-MSCs) transplantation has emerged as a promising therapeutic approach for SCA. The objectives of this study were to assess the feasibility, efficiency of hUC-MSCs transplantation in SCA3 and find the relative molecular mechanism.We perform this study with the B6.SCA3-YAC-84Q transgene mice as SCA3 model and resolve the under questions from entity to molecular level: 1. whether hUC-MSCs promote functional recovery and protect the SCA3 model from neuron loss by inhibiting the procedure of forming the neuronal intranuclear inclusions? 2. The pivotal role of paracrining function of hUC-MSCs in cure SCA3 mouse model. 3.Finding the relative molecular mechanisms of that hUC-MSCs could play a neuroprotection function in SCA3 mouse model. From all of the study, we may find a new therapeutic strategy for SCA3 and other polyglutamine diseases.

英文关键词： Spinocerebellar ataxia type 3；hUC-MSCs；neuronal intranuclear inclusions；70kD heat shock protein；apoptosis