PDF(Pubmed)
Abstract：
Neurodegenerative diseases (NDs) are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer\'s disease (AD), Parkinson\'s disease (PD), Huntington\'s disease (HD), and amyotrophic lateral sclerosis (ALS). Currently, there are no therapies available that can delay, stop, or reverse the pathological progression of NDs in clinical settings. As the population ages, NDs are imposing a huge burden on public health systems and affected families. Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments. While numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms, the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation gap. Old World non-human primates (NHPs), such as rhesus, cynomolgus, and vervet monkeys, are phylogenetically, physiologically, biochemically, and behaviorally most relevant to humans. This is particularly evident in the similarity of the structure and function of their central nervous systems, rendering such species uniquely valuable for neuroscience research. Recently, the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms. This review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained, as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.
神经退行性疾病 (Neurodegenerative diseases，ND) 是一类主要影响老年人群的神经疾病，包括阿尔茨海默病 (Alzheimer’s disease，AD)、帕金森病 (Parkinson’s disease，PD)、亨廷顿病 (Huntington’s disease，HD) 和肌萎缩侧索硬化症 (Amyotrophic lateral sclerosis，ALS)。目前，临床上尚无可以延迟、阻止或逆转 ND 病理进展的疗法。随着人口老龄化，ND 给公共卫生系统和患者家庭带来巨大负担。动物模型是临床前研究了解疾病发病机制和测试潜在治疗方法的重要工具。虽然已经开发出许多神经退行性疾病的啮齿类动物模型，并极大地增强了我们对疾病机制的理解，但动物模型的研究结果临床转化效果低下，这表明仍然需要弥合临床前研究和临床研究之间的差距。旧大陆非人类灵长类动物（non-human primates，NHPs），如恒河猴、食蟹猴和黑长尾猴，在系统发育、生理、生化和行为上，特别是在中枢神经系统结构和功能方面与人类最为接近，这使得它们对神经科学的研究具有重要作用。最近，已经有几种神经退行性疾病的转基因 NHP 模型报道，它们复刻了关键病理学指征并揭示了新的分子机制。在这篇综述中，我们描述了 NHP 模拟 ND 的能力以及来自这些 NHP 模型的新病理学见解。我们还讨论了模型制备及后续研究中面临的挑战。.
神经退行性疾病 (Neurodegenerative diseases，ND) 是一类主要影响老年人群的神经疾病，包括阿尔茨海默病 (Alzheimer’s disease，AD)、帕金森病 (Parkinson’s disease，PD)、亨廷顿病 (Huntington’s disease，HD) 和肌萎缩侧索硬化症 (Amyotrophic lateral sclerosis，ALS)。目前，临床上尚无可以延迟、阻止或逆转 ND 病理进展的疗法。随着人口老龄化，ND 给公共卫生系统和患者家庭带来巨大负担。动物模型是临床前研究了解疾病发病机制和测试潜在治疗方法的重要工具。虽然已经开发出许多神经退行性疾病的啮齿类动物模型，并极大地增强了我们对疾病机制的理解，但动物模型的研究结果临床转化效果低下，这表明仍然需要弥合临床前研究和临床研究之间的差距。旧大陆非人类灵长类动物（non-human primates，NHPs），如恒河猴、食蟹猴和黑长尾猴，在系统发育、生理、生化和行为上，特别是在中枢神经系统结构和功能方面与人类最为接近，这使得它们对神经科学的研究具有重要作用。最近，已经有几种神经退行性疾病的转基因 NHP 模型报道，它们复刻了关键病理学指征并揭示了新的分子机制。在这篇综述中，我们描述了 NHP 模拟 ND 的能力以及来自这些 NHP 模型的新病理学见解。我们还讨论了模型制备及后续研究中面临的挑战。.
摘要：
暂无翻译
