Brain-Derived Neurotrophic Factor and Stem Cell-Based Technologies in Huntington’s Disease Therapy

I. Kerkis, Joyce Macedo da Silva, C. Wenceslau, N. C. Mambelli-Lisboa, E. Frare
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引用次数: 3

Abstract

Neurodegenerative disorders, such as Huntington’s disease (HD), Alzheimer’s disease (AD), and Parkinson’s disease (PD), are characterized by changes in the levels and activities of neurotrophic factors (NTFs), such as brain-derived neurotrophic factor (BDNF). Gain-of-function and loss-of-function experiments demonstrate in fact the linkage between wild-type huntingtin (HTT) and gene transcription and intracellular transport of BDNF. In the present chapter, we will analyze the involvement of BDNF in HD and other neurodegenerative diseases. We will discuss the current BDNF technologies focusing on stem cell therapies that induce BDNF upregulation, for instance, the method of autologous mesenchymal stem cell (MSC) culturing in the presence of cocktail of BDNF inducers and factors (MSC/BDNF), genetic engineering of MSC and their use as a vector for BDNF gene delivery, and combined method of establishment of embryonic stem cell (ESC)-derived BDNF-overexpressing neural progenitors, which is still at the preclinical stage. Clinical trial that uses MSC/BDNF is already in course, while genetic engineering of MSC/BDNF is in perspective to treat adult and juvenile HD. The potential application of these technologies is beyond HD. Other neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases also can be further included in the list of clinical trials that use MSC/BDNF or even ESC/BDNF-overexpressing neural progenitors.
脑源性神经营养因子和干细胞技术在亨廷顿病治疗中的应用
神经退行性疾病,如亨廷顿病(HD)、阿尔茨海默病(AD)和帕金森病(PD),其特征是神经营养因子(NTFs)水平和活动的变化,如脑源性神经营养因子(BDNF)。功能获得和功能丧失实验实际上证明了野生型亨廷顿蛋白(HTT)与BDNF的基因转录和细胞内转运之间的联系。在本章中,我们将分析BDNF在HD和其他神经退行性疾病中的作用。我们将讨论目前的BDNF技术,重点是诱导BDNF上调的干细胞治疗,例如,在BDNF诱导剂和因子的混合物(MSC/BDNF)存在下的自体间充质干细胞(MSC)培养方法,MSC基因工程及其作为BDNF基因传递载体的方法,以及仍处于临床前阶段的胚胎干细胞(ESC)衍生的过表达BDNF的神经祖细胞的联合建立方法。使用MSC/BDNF的临床试验已经在进行中,而MSC/BDNF的基因工程有望治疗成人和青少年HD。这些技术的潜在应用范围超出了高清。其他神经退行性疾病,如阿尔茨海默病和帕金森病,也可以进一步纳入使用MSC/BDNF甚至ESC/BDNF过表达神经祖细胞的临床试验列表。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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