1. 7,8-Dihydroxycoumarin Alleviates Synaptic Loss by Activated PI3K-Akt-CREB-BDNF Signaling in Alzheimer's Disease Model Mice.
- Author
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Yan L, Jin Y, Pan J, He X, Zhong S, Zhang R, Choi L, Su W, and Chen J
- Subjects
- Amyloid Precursor Protein Secretases, Amyloid beta-Peptides genetics, Amyloid beta-Peptides metabolism, Animals, Aspartic Acid Endopeptidases therapeutic use, Brain-Derived Neurotrophic Factor genetics, Brain-Derived Neurotrophic Factor metabolism, Coumarins pharmacology, Disease Models, Animal, Memory Disorders drug therapy, Mice, Phosphatidylinositol 3-Kinases genetics, Phosphatidylinositol 3-Kinases metabolism, Proto-Oncogene Proteins c-akt genetics, Umbelliferones, Alzheimer Disease drug therapy, Alzheimer Disease genetics, Alzheimer Disease metabolism
- Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and is clinically characterized by the impairment of memory and cognition. Accumulation of β-amyloid (Aβ) 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 Aβ 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 Aβ deposition and synaptic loss in the process of treating AD.
- Published
- 2022
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