Abl depletion via autophagy mediates the beneficial effects of quercetin against Alzheimer pathology across species
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ABSTRACT:
PROVIDER: PRJNA985455 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24966953.fastq.gz | Fastqsanger.gz | |||
| SRR24966954.fastq.gz | Fastqsanger.gz | |||
| SRR24966955.fastq.gz | Fastqsanger.gz | |||
| SRR24966956.fastq.gz | Fastqsanger.gz | |||
| SRR24966957.fastq.gz | Fastqsanger.gz |
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Project description:Alzheimer's disease is the most common age-associated neurodegenerative disorder and the most frequent form of dementia in our society. Aging is a complex biological process concurrently shaped by genetic, dietary and environmental factors and natural compounds are emerging for their beneficial effects against age-related disorders such as cancer or cardiovascular diseases. Besides their antioxidant activity often described in simple model organisms, the molecular mechanisms underlying the beneficial effects of different dietary compounds remain largely unknown. Here, we exploited widely established C. elegans models for AD to test the effects of different natural compounds in vivo and focused on mechanistic aspects of one of them, quercetin, using complementary systems and assays. We show that quercetin has evolutionarily conserved beneficial effects against AD pathology: it prevents Aβ-induced detrimental effects in different C. elegans AD models and it reduces Aβ-secretion in mammalian cells. Mechanistically, we found that the beneficial effects of quercetin are mediated by autophagy-dependent reduced expression of Abl tyrosine kinase. In turn, autophagy is required upon Abl suppression to mediate quercetin’s protective effects against Aβ toxicity. Our data support the power of C. elegans as an in vivo model to investigate therapeutic options for Alzheimer disease.
2023-10-26 | GSE235199 | GEO
Project description:Alzheimer's disease is the most common age-associated neurodegenerative disorder and the most frequent form of dementia in our society. Aging is a complex biological process concurrently shaped by genetic, dietary and environmental factors and natural compounds are emerging for their beneficial effects against age-related disorders. Besides their antioxidant activity often described in simple model organisms, the molecular mechanisms underlying the beneficial effects of different dietary compounds remain however largely unknown. In the present study, we exploit the nematode Caenorhabditis elegans as a widely established model for aging studies, to test the effects of different natural compounds in vivo and focused on mechanistic aspects of one of them, quercetin, using complementary systems and assays. We show that quercetin has evolutionarily conserved beneficial effects against Alzheimer's disease (AD) pathology: it prevents Amyloid beta (Aβ)-induced detrimental effects in different C. elegans AD models and it reduces Aβ-secretion in mammalian cells. Mechanistically, we found that the beneficial effects of quercetin are mediated by autophagy-dependent reduced expression of Abl tyrosine kinase. In turn, autophagy is required upon Abl suppression to mediate quercetin's protective effects against Aβ toxicity. Our data support the power of C. elegans as an in vivo model to investigate therapeutic options for AD.
| S-EPMC10576830 | biostudies-literature
Project description:Quercetin has been described to have a wide range of beneficial effects in humans, ranging from anti-carcinogenic properties to reduced risk of cardiovascular disease. We tested whether a daily supplementation of quercetin leads to reproducible changes in gene expression profiles of human monocytes. Keywords: individual compound treatment
2009-12-10 | GSE13899 | GEO
Project description:Quercetin has been described to have a wide range of beneficial effects in humans, ranging from anti-carcinogenic properties to reduced risk of cardiovascular disease. We tested whether a daily supplementation of quercetin leads to reproducible changes in gene expression profiles of human monocytes. Experiment Overall Design: CD14+ monocytes were isolated from three healthy volunteers before and after a 2 wk supplementation period of 150mg quercetin per day. With this design every subject served as his or her own control (baseline sample = control)
2009-12-19 | E-GEOD-13899 | biostudies-arrayexpress
Project description:Microglia activation is a hallmark in Alzheimer Disease. Non-active and Active microglia were isolated from young and aged WT mice and before- and after- pathology mouse models of Alzheimer Disease. Microarray analysis was used to determine the global gene expression programe in microglia during pathological (Abeta or TAU pathology) versus control state.
2021-03-03 | GSE129296 | GEO
Project description:Adult stem cells undergo functional degeneration during aging. Quercetin exhibits many beneficial effects against aging and aging-related diseases. Using Drosophila as a model, we explore the efficacy of quercetin against adult stem cell aging and provide effective and feasible therapeutic solutions for preventing the aging-related functional decline of stem cells.
2022-12-06 | GSE216546 | GEO
Project description:High levels of oxidative stress and an associated neuronal DDR occur at the earliest stages of Alzheimer pathology (low Braak stage), and is associated with cognitive impairment. The aim of the present study was to combine immuno-LCM and microarray analysis to characterize the neuronal transcriptome at low Braak stages (Braak 0-II), with respect to the neuronal DDR, in post-mortem human frontal cortex derived from the Medical Research Council Cognitive Function and Ageing Study (MRC-CFAS).
2015-06-02 | GSE66333 | GEO
Project description:Elevated circulating lipid levels are known risk factors for cardiovascular diseases (CVD). In order to examine the effects of quercetin on hepatic lipid metabolism and detailed serum lipid profiles, mice received a mild-high-fat diet without (control) or with supplementation of 0.33% (w/w) quercetin for 12 weeks. Gas chromatography and 1H nuclear magnetic resonance were used to measure quantitatively serum lipid profiles and whole genome microarray analysis was used to identify the responsible mechanisms in liver. There were no significant differences found in mean body weight, energy intake and hepatic lipid accumulation between the quercetin and control group. In serum of quercetin-fed mice, TG levels were decreased with 15%, poly unsaturated fatty acids (PUFA) were increased with 14% and saturated fatty acids were decreased. Palmitic acid, oleic acid, and linoleic acid were all decreased in quercetin-fed mice by 9-15%. Both palmitic acid and oleic acid can be oxidized by omega-oxidation. Indeed, gene expression profiling showed that quercetin increased hepatic lipid metabolism, especially omega-oxidation. At the gene level, this was reflected by the up regulation of cytochrome P450 (Cyp) 4a10, Cyp4a14, Cyp4a31 and Acyl-CoA thioesterase 3 (Acot3). Two relevant regulators, Cytochrome P450 oxidoreductase (Por, rate limiting for cytochrome P450s) and the transcription factor Constitutive androstane receptor (Car; official symbol Nr1i3) were also up regulated in the quercetin-fed mice. We conclude that quercetin intake increased hepatic lipid omega-oxidation and lowered corresponding circulating lipid levels, a process that may involve Por and Car, and results in a potential beneficial CVD preventive effect.
2013-02-05 | GSE39140 | GEO
Project description:Elevated circulating lipid levels are known risk factors for cardiovascular diseases (CVD). In order to examine the effects of quercetin on hepatic lipid metabolism and detailed serum lipid profiles, mice received a mild-high-fat diet without (control) or with supplementation of 0.33% (w/w) quercetin for 12 weeks. Gas chromatography and 1H nuclear magnetic resonance were used to measure quantitatively serum lipid profiles and whole genome microarray analysis was used to identify the responsible mechanisms in liver. There were no significant differences found in mean body weight, energy intake and hepatic lipid accumulation between the quercetin and control group. In serum of quercetin-fed mice, TG levels were decreased with 15%, poly unsaturated fatty acids (PUFA) were increased with 14% and saturated fatty acids were decreased. Palmitic acid, oleic acid, and linoleic acid were all decreased in quercetin-fed mice by 9-15%. Both palmitic acid and oleic acid can be oxidized by omega-oxidation. Indeed, gene expression profiling showed that quercetin increased hepatic lipid metabolism, especially omega-oxidation. At the gene level, this was reflected by the up regulation of cytochrome P450 (Cyp) 4a10, Cyp4a14, Cyp4a31 and Acyl-CoA thioesterase 3 (Acot3). Two relevant regulators, Cytochrome P450 oxidoreductase (Por, rate limiting for cytochrome P450s) and the transcription factor Constitutive androstane receptor (Car; official symbol Nr1i3) were also up regulated in the quercetin-fed mice. We conclude that quercetin intake increased hepatic lipid omega-oxidation and lowered corresponding circulating lipid levels, a process that may involve Por and Car, and results in a potential beneficial CVD preventive effect. Liver samples were obtained from 36 C57BL/6J male adult mice. All mice started with a three week adaptation phase, in which they were fed a mild-high-fat diet. 12 mice were sacrificed immediately after the adaptation phase (t=0). The other 24 mice received the mild-high-fat diet without (HF) or with supplementation of 0.33% (w/w) quercetin (HF-Q) for 12 weeks.
2013-02-05 | E-GEOD-39140 | biostudies-arrayexpress
Project description:This study explores how quercetin may treat endometriosis (EMs) by combining network pharmacology and transcriptome sequencing approaches. Through network pharmacology, 132 shared targets between quercetin and EMs were identified, with KEGG pathway analysis suggesting that the MAPK signaling pathway could be a significant therapeutic target. Transcriptome sequencing revealed that PDGFRB was highly expressed in ectopic endometrial tissue, a finding confirmed by immunohistochemistry (IHC) showing elevated levels of PDGFRB, RAS, RAF1, and ERK1/2 in ectopic lesions. In an EMs mouse model, quercetin treatment led to a marked reduction in ectopic lesion volume, lowered adhesion scores, and decreased expression of PDGFRB, RAS, RAF1, and ERK1/2 in endometrial tissues. Additionally, the knockdown of PDGFRB in endometriosis cells inhibited their proliferation, invasion, and migration, processes critical to EMs pathology. Quercetin treatment further suppressed cell viability and downregulated the protein expression of RAS, phosphorylated RAF1, RAF1, phosphorylated ERK, and ERK1/2. These findings collectively suggest that quercetin exerts its therapeutic effect in endometriosis by regulating the MAPK signaling pathway via PDGFRB, thereby reducing EMs cell proliferation, invasion, and migration. This study provides insights into quercetin’s multi-targeted mechanism of action in endometriosis treatment.
2024-11-16 | GSE281569 | GEO