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Keywords = Isobavachin

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19 pages, 8724 KB  
Article
Discovery of Isobavachin, a Natural Flavonoid, as an Apolipoprotein E4 (ApoE4) Structure Corrector for Alzheimer’s Disease
by Sachin P. Patil, Bella R. Kuehn, Christina McCullough, Dean Bates, Hadil Hazim, Mamadou Diallo and Naomie Francois
Molecules 2025, 30(4), 940; https://doi.org/10.3390/molecules30040940 - 18 Feb 2025
Cited by 3 | Viewed by 2795
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by extensive neurodegeneration and consequent severe memory loss. Apolipoprotein E4 (ApoE4) is the strongest genetic risk factor for AD, with its pathological effects linked to structural instability and altered interactions with lipids and other [...] Read more.
Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by extensive neurodegeneration and consequent severe memory loss. Apolipoprotein E4 (ApoE4) is the strongest genetic risk factor for AD, with its pathological effects linked to structural instability and altered interactions with lipids and other important disease proteins including amyloid beta (Aβ) and tau (τ). Therefore, correcting and stabilizing the ApoE4 structure has emerged as a promising therapeutic strategy for mitigating its detrimental effects. In this study, we investigated naturally occurring bioavailable flavonoids as ApoE4 stabilizers, focusing on their potential to modulate ApoE4 structure and function. A comprehensive investigation of a focused database using our integrated computational and experimental screening protocol led to the identification of Isobavachin as a potential corrector and stabilizer of ApoE4 structure. In addition, a few other bioavailable flavonoids with similar stabilizing properties were identified, albeit to a much lesser extent as compared to Isobavachin. The findings support the therapeutic potential of flavonoids as ApoE4 modulators and highlight Isobavachin as a lead candidate for further preclinical evaluation. These results provide new insights into the pharmacological targeting of ApoE4 and open avenues for the development of flavonoid-based, ApoE-directed therapies for AD. Full article
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