A.N. Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Leninsky Ave. 33/2, 119071 Moscow, Russia.
Int J Mol Sci. 2023 Jun 6;24(12):9791. doi: 10.3390/ijms24129791.
Alzheimer's disease (AD) is an age-related, multifaceted neurological disorder associated with accumulation of aggregated proteins (amyloid Aβ and hyperphosphorylated tau), loss of synapses and neurons, and alterations in microglia. AD was recognized by the World Health Organization as a global public health priority. The pursuit of a better understanding of AD forced researchers to pay attention to well-defined single-celled yeasts. Yeasts, despite obvious limitations in application to neuroscience, show high preservation of basic biological processes with all eukaryotic organisms and offer great advantages over other disease models due to the simplicity, high growth rates on low-cost substrates, relatively simple genetic manipulations, the large knowledge base and data collections, and availability of an unprecedented amount of genomic and proteomic toolboxes and high-throughput screening techniques, inaccessible to higher organisms. Research reviewed above clearly indicates that yeast models, together with other, more simple eukaryotic models including animal models, and , significantly contributed to understanding Aβ and tau biology. These models allowed high throughput screening of factors and drugs that interfere with Aβ oligomerization, aggregation and toxicity, and tau hyperphosphorylation. In the future, yeast models will remain relevant, with a focus on creating novel high throughput systems to facilitate the identification of the earliest AD biomarkers among different cellular networks in order to achieve the main goal-to develop new promising therapeutic strategies to treat or prevent the disease.
阿尔茨海默病(AD)是一种与聚集蛋白(淀粉样蛋白 Aβ和过度磷酸化的 tau)、突触和神经元丧失以及小胶质细胞改变相关的与年龄相关的多方面神经退行性疾病。AD 被世界卫生组织(WHO)认为是全球公共卫生重点关注的问题。为了更好地了解 AD,研究人员不得不关注定义明确的单细胞酵母。酵母虽然在应用于神经科学方面存在明显的局限性,但与所有真核生物一样,高度保留了基本的生物学过程,并具有许多优于其他疾病模型的优势,因为酵母具有简单、在低成本基质上的高增长率、相对简单的遗传操作、庞大的知识库和数据集以及前所未有的基因组和蛋白质组工具盒和高通量筛选技术,这些都是高等生物所不具备的。上述研究清楚地表明,酵母模型与包括动物模型在内的其他更简单的真核模型一起,为理解 Aβ 和 tau 生物学做出了重要贡献。这些模型允许对干扰 Aβ 寡聚、聚集和毒性以及 tau 过度磷酸化的因素和药物进行高通量筛选。在未来,酵母模型仍将具有相关性,重点是创建新的高通量系统,以促进在不同细胞网络中识别最早的 AD 生物标志物,从而实现主要目标——开发新的有前途的治疗策略来治疗或预防该疾病。