Expression data of FMN supplementation from Saccharomyces cerevisiae

Alzheimer’s disease (AD) is hallmarked by progressive neurodegeneration. Aggregation of amyloid-β peptides (Aβ) is thought to play a pivotal role in driving AD pathogenesis, yet the underlying mechanisms remain unclear. Here, we use yeast genome-scale screening to study global synthetic genetic interactions and identify toxicity modifiers of Aβ42. We find that the gene encoding riboflavin kinase (FMN1) and its metabolic product flavin mononucleotide (FMN) are connected to AD. These relationship between Aβ42 and FMN was previously unknown. As a cofactor for flavoenzymes, FMN supplementation appears to attune many cellular processes to ameliorate Aβ42 toxicity. RNA-seq analysis further confirms FMN’s cytoprotective mechanisms. Our findings provide increased understanding of FMN regulated cellular pathways which are associated with potential targets for AD treatment.阿尔茨海默病（Alzheimer’s disease, AD）以进行性神经退行性病变为核心特征。淀粉样β肽（amyloid-β peptides, Aβ）的聚集被认为在AD发病机制中发挥关键驱动作用，但其具体潜在分子机制仍未明确。本研究借助酵母全基因组规模筛选技术，对全局合成遗传相互作用展开研究，并鉴定出Aβ42的毒性修饰因子。研究发现，编码核黄素激酶（riboflavin kinase, FMN1）的基因及其代谢产物黄素单核苷酸（flavin mononucleotide, FMN）与AD存在关联——这一Aβ42与FMN之间的联系此前尚未被报道。作为黄素酶的辅酶，补充FMN可通过协调多种细胞进程以减轻Aβ42的毒性。RNA测序（RNA-seq）分析进一步验证了FMN的细胞保护作用机制。本研究结果深化了对FMN调控的细胞通路的认知，这些通路有望成为AD治疗的潜在靶点。