FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3122386171> ?p ?o ?g. }

• W3122386171 endingPage "42" @default.
• W3122386171 startingPage "33" @default.
• W3122386171 abstract "Mitochondrial diseases (MDs) are a heterogeneous group of disorders resulting from mutations in nuclear or mitochondrial DNA genes encoding mitochondrial proteins1,2. MDs cause pathologies with severe tissue damage and ultimately death3,4. There are no cures for MDs and current treatments are only palliative5-7. Here we show that tetracyclines improve fitness of cultured MD cells and ameliorate disease in a mouse model of Leigh syndrome. To identify small molecules that prevent cellular damage and death under nutrient stress conditions, we conduct a chemical high-throughput screen with cells carrying human MD mutations and discover a series of antibiotics that maintain survival of various MD cells. We subsequently show that a sub-library of tetracycline analogues, including doxycycline, rescues cell death and inflammatory signatures in mutant cells through partial and selective inhibition of mitochondrial translation, resulting in an ATF4-independent mitohormetic response. Doxycycline treatment strongly promotes fitness and survival of Ndufs4-/- mice, a preclinical Leigh syndrome mouse model8. A proteomic analysis of brain tissue reveals that doxycycline treatment largely prevents neuronal death and the accumulation of neuroimmune and inflammatory proteins in Ndufs4-/- mice, indicating a potential causal role for these proteins in the brain pathology. Our findings suggest that tetracyclines deserve further evaluation as potential drugs for the treatment of MDs." @default.
• W3122386171 created "2021-02-01" @default.
• W3122386171 creator A5011786330 @default.
• W3122386171 creator A5021576499 @default.
• W3122386171 creator A5022868232 @default.
• W3122386171 creator A5023696637 @default.
• W3122386171 creator A5040754312 @default.
• W3122386171 creator A5041955512 @default.
• W3122386171 creator A5044727261 @default.
• W3122386171 creator A5069373190 @default.
• W3122386171 creator A5077311072 @default.
• W3122386171 creator A5079793809 @default.
• W3122386171 creator A5084410272 @default.
• W3122386171 creator A5085940421 @default.
• W3122386171 creator A5090257447 @default.
• W3122386171 date "2021-01-18" @default.
• W3122386171 modified "2023-10-17" @default.
• W3122386171 title "Tetracyclines promote survival and fitness in mitochondrial disease models" @default.
• W3122386171 cites W1484678674 @default.
• W3122386171 cites W1551444218 @default.
• W3122386171 cites W1635459918 @default.
• W3122386171 cites W1970554352 @default.
• W3122386171 cites W1973260880 @default.
• W3122386171 cites W1980496079 @default.
• W3122386171 cites W1984538590 @default.
• W3122386171 cites W1988565273 @default.
• W3122386171 cites W1996317585 @default.
• W3122386171 cites W1999014597 @default.
• W3122386171 cites W2007636933 @default.
• W3122386171 cites W2018576241 @default.
• W3122386171 cites W2027320048 @default.
• W3122386171 cites W2041399392 @default.
• W3122386171 cites W2050254109 @default.
• W3122386171 cites W2066650294 @default.
• W3122386171 cites W2072404701 @default.
• W3122386171 cites W2076174072 @default.
• W3122386171 cites W2077926137 @default.
• W3122386171 cites W2094618868 @default.
• W3122386171 cites W2113407336 @default.
• W3122386171 cites W2122037893 @default.
• W3122386171 cites W2129181731 @default.
• W3122386171 cites W2132820862 @default.
• W3122386171 cites W2133465414 @default.
• W3122386171 cites W2142479657 @default.
• W3122386171 cites W2142845824 @default.
• W3122386171 cites W2147312658 @default.
• W3122386171 cites W2152904546 @default.
• W3122386171 cites W2156994528 @default.
• W3122386171 cites W2158217645 @default.
• W3122386171 cites W2160806578 @default.
• W3122386171 cites W2167627444 @default.
• W3122386171 cites W2174487690 @default.
• W3122386171 cites W2300647592 @default.
• W3122386171 cites W2305670323 @default.
• W3122386171 cites W2401348667 @default.
• W3122386171 cites W2412031353 @default.
• W3122386171 cites W2419535666 @default.
• W3122386171 cites W2460752692 @default.
• W3122386171 cites W2521735958 @default.
• W3122386171 cites W2558041282 @default.
• W3122386171 cites W2586731249 @default.
• W3122386171 cites W2606524946 @default.
• W3122386171 cites W2612960139 @default.
• W3122386171 cites W2618870156 @default.
• W3122386171 cites W2739804116 @default.
• W3122386171 cites W2740717097 @default.
• W3122386171 cites W2742984768 @default.
• W3122386171 cites W2757601540 @default.
• W3122386171 cites W2763498391 @default.
• W3122386171 cites W2784734859 @default.
• W3122386171 cites W2806312996 @default.
• W3122386171 cites W2887997888 @default.
• W3122386171 cites W2896581442 @default.
• W3122386171 cites W2900128053 @default.
• W3122386171 cites W2908521178 @default.
• W3122386171 cites W2942228202 @default.
• W3122386171 cites W2951305777 @default.
• W3122386171 cites W2981193232 @default.
• W3122386171 cites W3006301159 @default.
• W3122386171 cites W3010985052 @default.
• W3122386171 cites W3013061819 @default.
• W3122386171 cites W3014091950 @default.
• W3122386171 cites W3029697906 @default.
• W3122386171 cites W3083406432 @default.
• W3122386171 cites W4210476933 @default.
• W3122386171 cites W4231604814 @default.
• W3122386171 doi "https://doi.org/10.1038/s42255-020-00334-y" @default.
• W3122386171 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7856165" @default.
• W3122386171 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33462515" @default.
• W3122386171 hasPublicationYear "2021" @default.
• W3122386171 type Work @default.
• W3122386171 sameAs 3122386171 @default.
• W3122386171 citedByCount "32" @default.
• W3122386171 countsByYear W31223861712021 @default.
• W3122386171 countsByYear W31223861712022 @default.
• W3122386171 countsByYear W31223861712023 @default.
• W3122386171 crossrefType "journal-article" @default.
• W3122386171 hasAuthorship W3122386171A5011786330 @default.

• next