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00925njm 22002777a 4500 dc Carmona Mata, Vanesa author Martín-Aragón Álvarez, Sagrario author Goldberg, Joshua author Schubert, David author Bermejo Bescos, María De La Paloma author 2018 Long-term consumption of phytochemicals has been associated with a decreased risk of dementia. The modes of action of two flavonols (morin and isoquercitrin) and two flavanones (hesperidin and neohesperidin) were characterized as single-compound drugs in several Alzheimer's disease (AD)-related assays. First, these phytochemicals were assayed in an amyloid toxicity model (MC65 cells). Second, we examined the activity of the flavonoids in cell-free assays against β- and γ-secretases and acetylcholinesterase activities, as well as agents able to modify the fibrillogenesis of the amyloid β-peptide. Additionally, they were assayed against glutamate-induced oxytosis, as scavengers of reactive oxygen species (ROS), as inhibitors of caspase-3, -8 and -9 activation and as modulators of the chymotrypsin-like activity of the ubiquitin-proteasome system. Morin and isoquercitrin, unlike flavanones, exhibited significant activities as β- and γ-secretase inhibitors, as well as capacity to inhibit Aβ aggregation and favor its disaggregation. Flavonols and flavanones showed ROS scavenger activity (P < 0.05), attenuation of caspase-3 and -9 activation (P < 0.05) and restoration of the reduced chymotrypsin-like activity of proteasome 20S (P < 0.05) upon H2O2 exposure of APPswe cells. Flavanones failed to protect against glutamate-induced oxytosis. These findings provide new insight into the anti-amyloidogenic effects of morin and isoquercitrin. Carmona V, Martín-Aragón S, Goldberg J, Schubert D, Bermejo-Bescós P. Several targets involved in Alzheimer's disease amyloidogenesis are affected by morin and isoquercitrin. Nutr Neurosci. 2020 Aug;23(8):575-590. 1028-415X 10.1080/1028415x.2018.1534793 https://hdl.handle.net/20.500.14352/93272 1476-8305 https://doi.org/10.1080/1028415X.2018.1534793 Several targets involved in Alzheimer’s disease amyloidogenesis are affected by morin and isoquercitrin