The lack of effective therapies that slow the progression of Alzheimer’s disease (AD) and related tauopathies highlights the need for a more comprehensive understanding of the fundamental cellular mechanisms underlying these diseases. Model organisms, including yeast, worms, and flies, provide simple systems with which to investigate the mechanisms of disease. The evolutionary conservation of cellular pathways regulating proteostasis and stress response in these organisms facilitates the study of genetic factors that contribute to, or protect against, neurodegeneration. Here, we review genetic modifiers of neurodegeneration and related cellular pathways identified in the budding yeast Saccharomyces cerevisiae, the nematode Caenorhabditis elegans, and the fruit fly Drosophila melanogaster, focusing on models of AD and related tauopathies. We further address the potential of simple model systems to better understand the fundamental mechanisms that lead to AD and other neurodegenerative disorders.

中文翻译：

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简单的模型系统揭示了阿尔茨海默病和相关tau蛋白病的保守机制

由于缺乏有效的疗法来减缓阿尔茨海默病 (AD) 和相关 tau蛋白病的进展，因此需要更全面地了解这些疾病的基本细胞机制。模型生物，包括酵母、蠕虫和苍蝇，提供了研究疾病机制的简单系统。这些生物体中调节蛋白质稳态和应激反应的细胞途径的进化保守性促进了对导致或预防神经变性的遗传因素的研究。在这里，我们回顾了在芽殖酵母酿酒酵母、线虫秀丽隐杆线虫和果蝇果蝇中发现的神经退行性疾病和相关细胞途径的遗传修饰剂，重点关注 AD 和相关 tau蛋白病的模型。我们进一步探讨了简单模型系统的潜力，以更好地理解导致 AD 和其他神经退行性疾病的基本机制。