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

• Published in: Cell death discovery Vol. 9; no. 1; p. 376
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14-10-2023; Springer Nature B.V; Nature Publishing Group
• Subjects: 631/378/2611; 692/308/1426; Aging; Alzheimer's disease; Apoptosis; Autophagy; Biochemistry; Biomedical and Life Sciences; Cell Biology; Cell Cycle Analysis; Dementia disorders; Environmental factors; Kinases; Life Sciences; Mammalian cells; Molecular modelling; Neurodegenerative diseases; Pathology; Protein-tyrosine kinase; Quercetin; Stem Cells; Toxicity; β-Amyloid
• ISSN: 2058-7716; 2058-7716
• DOI: 10.1038/s41420-023-01592-x

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.