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Abl depletion via autophagy mediates the beneficial effects of quercetin against Alzheimer pathology across species

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 effe...

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Autores principales: Schiavi, Alfonso, Cirotti, Claudia, Gerber, Lora-Sophie, Di Lauro, Giulia, Maglioni, Silvia, Shibao, Priscila Yumi Tanaka, Montresor, Sabrina, Kirstein, Janine, Petzsch, Patrick, Köhrer, Karl, Schins, Roel P. F., Wahle, Tina, Barilà, Daniela, Ventura, Natascia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10576830/
https://www.ncbi.nlm.nih.gov/pubmed/37838776
http://dx.doi.org/10.1038/s41420-023-01592-x
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author Schiavi, Alfonso
Cirotti, Claudia
Gerber, Lora-Sophie
Di Lauro, Giulia
Maglioni, Silvia
Shibao, Priscila Yumi Tanaka
Montresor, Sabrina
Kirstein, Janine
Petzsch, Patrick
Köhrer, Karl
Schins, Roel P. F.
Wahle, Tina
Barilà, Daniela
Ventura, Natascia
author_facet Schiavi, Alfonso
Cirotti, Claudia
Gerber, Lora-Sophie
Di Lauro, Giulia
Maglioni, Silvia
Shibao, Priscila Yumi Tanaka
Montresor, Sabrina
Kirstein, Janine
Petzsch, Patrick
Köhrer, Karl
Schins, Roel P. F.
Wahle, Tina
Barilà, Daniela
Ventura, Natascia
author_sort Schiavi, Alfonso
collection PubMed
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.
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spelling pubmed-105768302023-10-16 Abl depletion via autophagy mediates the beneficial effects of quercetin against Alzheimer pathology across species Schiavi, Alfonso Cirotti, Claudia Gerber, Lora-Sophie Di Lauro, Giulia Maglioni, Silvia Shibao, Priscila Yumi Tanaka Montresor, Sabrina Kirstein, Janine Petzsch, Patrick Köhrer, Karl Schins, Roel P. F. Wahle, Tina Barilà, Daniela Ventura, Natascia Cell Death Discov Article 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. Nature Publishing Group UK 2023-10-14 /pmc/articles/PMC10576830/ /pubmed/37838776 http://dx.doi.org/10.1038/s41420-023-01592-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Schiavi, Alfonso
Cirotti, Claudia
Gerber, Lora-Sophie
Di Lauro, Giulia
Maglioni, Silvia
Shibao, Priscila Yumi Tanaka
Montresor, Sabrina
Kirstein, Janine
Petzsch, Patrick
Köhrer, Karl
Schins, Roel P. F.
Wahle, Tina
Barilà, Daniela
Ventura, Natascia
Abl depletion via autophagy mediates the beneficial effects of quercetin against Alzheimer pathology across species
title Abl depletion via autophagy mediates the beneficial effects of quercetin against Alzheimer pathology across species
title_full Abl depletion via autophagy mediates the beneficial effects of quercetin against Alzheimer pathology across species
title_fullStr Abl depletion via autophagy mediates the beneficial effects of quercetin against Alzheimer pathology across species
title_full_unstemmed Abl depletion via autophagy mediates the beneficial effects of quercetin against Alzheimer pathology across species
title_short Abl depletion via autophagy mediates the beneficial effects of quercetin against Alzheimer pathology across species
title_sort abl depletion via autophagy mediates the beneficial effects of quercetin against alzheimer pathology across species
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10576830/
https://www.ncbi.nlm.nih.gov/pubmed/37838776
http://dx.doi.org/10.1038/s41420-023-01592-x
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