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FMN reduces Amyloid...
FMN reduces Amyloid-beta toxicity in yeast by regulating redox status and cellular metabolism
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- Chen, Xin, 1980 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Ji, Boyang, 1983 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Hao, Xinxin (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Centrum för åldrande och hälsa (AgeCap),Institute of Biomedicine,Centre for Ageing and Health (Agecap),University of Gothenburg
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- Li, Xiaowei, 1986 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Eisele, Frederik (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Centrum för åldrande och hälsa (AgeCap),Institute of Biomedicine,Centre for Ageing and Health (Agecap),University of Gothenburg
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- Nyström, Thomas, 1960 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Centrum för åldrande och hälsa (AgeCap),Institute of Biomedicine,Centre for Ageing and Health (Agecap),University of Gothenburg
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- Petranovic Nielsen, Dina, 1975 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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(creator_code:org_t)
- 2020-02-13
- 2020
- English.
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Abstract
Subject headings
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- Alzheimer's disease (AD) is defined by progressive neurodegeneration, with oligomerization and aggregation of amyloid-beta peptides (A beta) 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 A beta 42, using yeast as the model organism. We find that FMN1, the gene encoding riboflavin kinase, and its metabolic product flavin mononucleotide (FMN) reduce A beta 42 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 alpha-synuclein toxicity in the humanized yeast. Our findings offer insights for reducing cytotoxicity of A beta 42, and potentially other misfolded proteins, via FMN-dependent cellular pathways.Saccharomyces cerevisiae is a model organism to study proteins involved in neurodegeneration. Here, the authors performed a yeast genome-wide synthetic genetic interaction array (SGA) to screen for toxicity modifiers of A beta 42 and identify riboflavin kinase and its metabolic product flavin mononucleotide as modulators that alleviate cellular A beta 42 toxicity, which is supported by further experimental analyses.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Keyword
- oxidative stress
- alzheimers-disease
- saccharomyces-cerevisiae
- quality-control
- protein-kinase
- gene lists
- riboflavin
- aggregation
- rna
- neurodegeneration
- Science & Technology - Other Topics
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Chen, Xin, 1980
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Ji, Boyang, 1983
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Hao, Xinxin
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Li, Xiaowei, 198 ...
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Eisele, Frederik
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Nyström, Thomas, ...
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show more...
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Petranovic Niels ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Cell Biology
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
- Articles in the publication
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Nature Communica ...
- By the university
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University of Gothenburg
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Chalmers University of Technology