Marsh Samuel E, Blurton-Jones Mathew
Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA 92697, USA; Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA 92697, USA.
Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA 92697, USA; Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA 92697, USA; Department of Neurobiology & Behavior, University of California Irvine, Irvine, CA 92697, USA.
Neurochem Int. 2017 Jun;106:94-100. doi: 10.1016/j.neuint.2017.02.006. Epub 2017 Feb 20.
Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and Huntington's disease currently affect tens of millions of people worldwide. Unfortunately, as the world's population ages, the incidence of many of these diseases will continue to rise and is expected to more than double by 2050. Despite significant research and a growing understanding of disease pathogenesis, only a handful of therapies are currently available and all of them provide only transient benefits. Thus, there is an urgent need to develop novel disease-modifying therapies to prevent the development or slow the progression of these debilitating disorders. A growing number of pre-clinical studies have suggested that transplantation of neural stem cells (NSCs) could offer a promising new therapeutic approach for neurodegeneration. While much of the initial excitement about this strategy focused on the use of NSCs to replace degenerating neurons, more recent studies have implicated NSC-mediated changes in neurotrophins as a major mechanism of therapeutic efficacy. In this mini-review we will discuss recent work that examines the ability of NSCs to provide trophic support to disease-effected neuronal populations and synapses in models of neurodegeneration. We will then also discuss some of key challenges that remain before NSC-based therapies for neurodegenerative diseases can be translated toward potential clinical testing.
诸如阿尔茨海默病、帕金森病和亨廷顿病等神经退行性疾病目前在全球影响着数千万人。不幸的是，随着世界人口老龄化，这些疾病中的许多疾病的发病率将持续上升，预计到2050年将增加一倍多。尽管进行了大量研究且对疾病发病机制的理解不断加深，但目前仅有少数几种疗法，而且所有这些疗法都只能提供短暂的益处。因此，迫切需要开发新的疾病修饰疗法，以预防这些使人衰弱的疾病的发生或减缓其进展。越来越多的临床前研究表明，神经干细胞（NSC）移植可能为神经退行性变提供一种有前景的新治疗方法。虽然最初对该策略的很多兴奋点集中在使用神经干细胞来替代退化的神经元，但最近的研究表明，神经干细胞介导的神经营养因子变化是治疗效果的主要机制。在本综述中，我们将讨论最近的研究工作，这些工作研究了神经干细胞在神经退行性变模型中为受疾病影响的神经元群体和突触提供营养支持的能力。然后，我们还将讨论在基于神经干细胞的神经退行性疾病疗法能够转化为潜在的临床试验之前仍然存在的一些关键挑战。
