FMN reduces Amyloid-β toxicity in yeast by regulating redox status and cellular metabolism
Artikel i vetenskaplig tidskrift, 2020

Alzheimer's disease (AD) is defined by progressive neurodegeneration, with oligomerization and aggregation of amyloid-β peptides (Aβ) playing a pivotal role in its pathogenesis. In recent years, the yeast Saccharomyces cerevisiae has been successfully used to clarify the roles of different human proteins involved in neurodegeneration. Here, we report a genome-wide synthetic genetic interaction array to identify toxicity modifiers of Aβ42, using yeast as the model organism. We find that FMN1, the gene encoding riboflavin kinase, and its metabolic product flavin mononucleotide (FMN) reduce Aβ42 toxicity. Classic experimental analyses combined with RNAseq show the effects of FMN supplementation to include reducing misfolded protein load, altering cellular metabolism, increasing NADH/(NADH + NAD+) and NADPH/(NADPH + NADP+) ratios and increasing resistance to oxidative stress. Additionally, FMN supplementation modifies Htt103QP toxicity and α-synuclein toxicity in the humanized yeast. Our findings offer insights for reducing cytotoxicity of Aβ42, and potentially other misfolded proteins, via FMN-dependent cellular pathways.

Författare

Xin Chen

Chalmers, Biologi och bioteknik, Systembiologi

Boyang Ji

Chalmers, Biologi och bioteknik, Systembiologi

Xinxin Hao

Göteborgs universitet

Xiaowei Li

Chalmers, Biologi och bioteknik, Systembiologi

Frederik Eisele

Göteborgs universitet

Thomas Nyström

Göteborgs universitet

Dina Petranovic Nielsen

Chalmers, Biologi och bioteknik, Systembiologi

Nature Communications

2041-1723 (ISSN)

Vol. 11 1 867-

Ämneskategorier

Cellbiologi

Biokemi och molekylärbiologi

Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)

DOI

10.1038/s41467-020-14525-4

PubMed

32054832

Mer information

Senast uppdaterat

2020-04-03