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| Status |
Public on Oct 26, 2023 |
| Title |
Abl depletion via autophagy mediates the beneficial effects of quercetin against Alzheimer pathology across species |
| Organism |
Caenorhabditis elegans |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
Worms were collected on day 3 after birth, with 5 independent replicates performed for both control and quercetin treated groups, while 4 independent replicates were performed for lutein.
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| Contributor(s) |
Schiavi A, Cirotti C, Gerber L, Lauro GD, Maglioni S, Petzsch P, Köhrer K, Schins RP, Wahle T, Barilà D, Ventura N |
| Citation(s) |
37838776 |
| Submission date |
Jun 20, 2023 |
| Last update date |
Oct 26, 2023 |
| Contact name |
Natascia Ventura |
| Organization name |
Heinrich Heine University and the IUF- Leibniz Research Institute for Environmental Medicine
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| Street address |
Auf'm Hennekamp 50
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| City |
Düsseldorf |
| ZIP/Postal code |
40225 |
| Country |
Germany |
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| Platforms (1) |
| GPL24892 |
Illumina HiSeq 3000 (Caenorhabditis elegans) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA985455 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE235199_Experiment_processed_data.xlsx |
6.2 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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