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J Agric Food Chem ; 70(23): 7130-7138, 2022 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-35657168

RESUMEN

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and is clinically characterized by the impairment of memory and cognition. Accumulation of ß-amyloid (Aß) in the brain is considered as a key process in the development of AD because it impairs the synapses' function to impair memory formation. Recent research studies have indicated that a group of edible plant-derived Thymelaeaceae compounds known as coumarin may exert particularly powerful actions on alleviating learning and memory impairment. 7,8-Dithydroxycoumarin (7,8-DHC), a bioactive component of coumarin derived from Thymelaeaceae, showed its function in neuroprotection before. In this study, we found that 7,8-DHC was able to mitigate Aß accumulation via reducing the level of BACE1 and increasing the level of ADAM17 and ADAM10. More importantly, we found that 7,8-DHC could mitigate memory impairment, promote the dendrite branch density, and increase synaptic protein expression via activating PI3K-Akt-CREB-BDNF signaling. Hence, these results suggested that 7,8-DHC represented a novel bioactive therapeutic agent in mitigating Aß deposition and synaptic loss in the process of treating AD.


Asunto(s)
Enfermedad de Alzheimer , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Secretasas de la Proteína Precursora del Amiloide , Péptidos beta-Amiloides/genética , Péptidos beta-Amiloides/metabolismo , Animales , Ácido Aspártico Endopeptidasas/uso terapéutico , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Cumarinas/farmacología , Modelos Animales de Enfermedad , Trastornos de la Memoria/tratamiento farmacológico , Ratones , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Umbeliferonas
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