Hayden Ashley N, Leptich Emily J, Arey Rachel N
Center for Precision Environmental Health, Baylor College of Medicine, Houston, TX 77030, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
Center for Precision Environmental Health, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Comp Biochem Physiol A Mol Integr Physiol. 2022 May;267:111166. doi: 10.1016/j.cbpa.2022.111166. Epub 2022 Feb 14.
As human life expectancy increases, neurodegenerative diseases present a growing public health threat, for which there are currently few effective treatments. There is an urgent need to understand the molecular and genetic underpinnings of these disorders so new therapeutic targets can be identified. Here we present the argument that the simple nematode worm Caenorhabditis elegans is a powerful tool to rapidly study neurodegenerative disorders due to their short lifespan and vast array of genetic tools, which can be combined with characterization of conserved neuronal processes and behavior orthologous to those disrupted in human disease. We review how pre-existing C. elegans models provide insight into human neurological disease as well as an overview of current tools available to study neurodegenerative diseases in the worm, with an emphasis on genetics and behavior. We also discuss open questions that C. elegans may be particularly well suited for in future studies and how worms will be a valuable preclinical model to better understand these devastating neurological disorders.
随着人类预期寿命的增加，神经退行性疾病对公共卫生构成了日益严重的威胁，目前针对这些疾病的有效治疗方法很少。迫切需要了解这些疾病的分子和遗传基础，以便确定新的治疗靶点。在此，我们提出这样的观点：简单的线虫秀丽隐杆线虫是快速研究神经退行性疾病的有力工具，因为它们寿命短且拥有大量的遗传工具，这些工具可以与对保守神经元过程以及与人类疾病中被破坏的过程直系同源的行为的表征相结合。我们回顾了现有的秀丽隐杆线虫模型如何为人类神经系统疾病提供见解，以及目前用于研究线虫神经退行性疾病的工具概述，重点是遗传学和行为学。我们还讨论了秀丽隐杆线虫在未来研究中可能特别适合解决的开放性问题，以及线虫将如何成为一个有价值的临床前模型，以更好地理解这些毁灭性的神经系统疾病。
