Abstract:
In recent years, advances in science and technology have improved our quality of life, enabling us to tackle diseases and increase human life expectancy. However, longevity is accompanied by an accretion in the frequency of age-related neurodegenerative diseases, creating a growing burden, with pervasive social impact for human societies. The cost of managing such chronic disorders and the lack of effective treatments highlight the need to decipher their molecular and genetic underpinnings, in order to discover new therapeutic targets. In this effort, the nematode Caenorhabditis elegans serves as a powerful tool to recapitulate several disease-related phenotypes and provides a highly malleable genetic model that allows the implementation of multidisciplinary approaches, in addition to large-scale genetic and pharmacological screens. Its anatomical transparency allows the use of co-expressed fluorescent proteins to track the progress of neurodegeneration. Moreover, the functional conservation of neuronal processes, along with the high homology between nematode and human genomes, render C. elegans extremely suitable for the study of human neurodegenerative disorders. This review describes nematode models used to study neurodegeneration and underscores their contribution in the effort to dissect the molecular basis of human diseases and identify novel gene targets with therapeutic potential.
摘要:
近年来,科学技术的进步提高了我们的生活质量,使我们能够应对疾病并增加人类的预期寿命。然而,长寿伴随着与年龄相关的神经退行性疾病的频率增加,造成越来越大的负担,对人类社会有着普遍的社会影响。管理此类慢性疾病的成本和缺乏有效的治疗方法凸显了破译其分子和遗传基础的必要性,以发现新的治疗靶点。在这种努力中,线虫秀丽隐杆线虫是概括几种疾病相关表型的强大工具,并提供了一种高度可延展的遗传模型,允许实施多学科方法,除了大规模的遗传和药理筛选。它的解剖学透明度允许使用共表达的荧光蛋白来跟踪神经变性的进展。此外,神经元过程的功能保守性,以及线虫和人类基因组之间的高度同源性,使秀丽隐杆线虫非常适合人类神经退行性疾病的研究。这篇综述描述了用于研究神经变性的线虫模型,并强调了它们在解剖人类疾病的分子基础和鉴定具有治疗潜力的新基因靶标方面的贡献。