Abstract

Since Caenorhabditis elegans was first introduced as a genetic model organism by Sydney Brenner, researchers studying it have made significant contributions in numerous fields including investigations of the pathophysiology of neurodegenerative diseases. The simple anatomy, optical transparency, and short life-span of this small nematode together with the development and curation of many openly shared resources (including the entire genome, cell lineage and the neural map of the animal) allow researchers using C. elegans to move their research forward rapidly in an immensely collaborative community. These resources have allowed researchers to use C. elegans to study the cellular processes that may underlie human diseases. Indeed, many disease-associated genes have orthologs in C. elegans, allowing the effects of mutations in these genes to be studied in relevant and reproducible neuronal cell-types at single-cell resolution in vivo. Here we review studies that have attempted to establish genetic models of specific human neurodegenerative diseases (ALS, Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease) in C. elegans and what they have contributed to understanding the molecular and genetic underpinnings of each disease. With continuous advances in genome engineering, research conducted using this small organism first established by Brenner, Sulston and their contemporaries will continue to contribute to the understanding of human nervous diseases.

摘要

自从秀丽隐杆线虫被悉尼·布伦纳（Sydney Brenner）首次引入作为遗传模型生物以来，研究它的研究人员在许多领域都做出了重要贡献，包括神经退行性疾病的病理生理学研究。这种小线虫的简单解剖结构，光学透明度和较短的寿命，以及许多公开共享资源（包括整个基因组，细胞谱系和动物神经图谱）的开发和管理，使研究人员可以利用秀丽隐杆线虫进行在一个巨大的协作社区中迅速推动他们的研究。这些资源使研究人员可以使用秀丽隐杆线虫研究可能是人类疾病的细胞过程。实际上，许多与疾病相关的基因在秀丽隐杆线虫中具有直系同源物，从而可以在体内以单细胞分辨率研究相关和可再现的神经元细胞类型中这些基因突变的影响。在这里，我们审查了试图建立线虫的特定人类神经退行性疾病（ALS，阿尔茨海默氏病，帕金森氏病，亨廷顿氏病）的遗传模型的研究以及它们对理解每种疾病的分子和遗传基础所做的贡献。随着基因组工程技术的不断进步，使用这种由Brenner，Sulston及其同代人首先建立的小生物进行的研究将继续有助于人们对神经疾病的理解。