期刊
BIOMEDICINE & PHARMACOTHERAPY
卷 121, 期 -, 页码 -出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2019.109670
关键词
Alzheimer's disease; Berberine; Tau pathology; Autophagy
资金
- National Natural Science Foundation of China [81901422]
- Shenzhen Bureau of Science, Technology and Information [JCYJ20180307151246821]
- Project of Administration of Traditional Chinese Medicine of Guangdong Province of China [20181064]
- Project of Traditional Chinese Medicine of Guangming District [GM2019020029, GM2019020028]
Berberine is a natural isoquinoline alkaloid isolated from the Rhizoma coptidis. Recent advances in research throw more lights of its beneficial role towards Alzheimer's disease (AD), including promoting beta-amyloid (A beta) clearance, as well as inhibiting A beta production in the triple-transgenic mouse model of Alzheimer's disease (3xTg AD). However, it remains unclarified if berberine has an effect on tau pathology. According to our study, berberine did not only significantly improve 3xTg AD mice's spatial learning capacity and memory retentions, but also attenuated the hyperphosphorylation of tau. via modulating the activity of Akt/glycogen synthase kinase-3 beta and protein phosphatase 2A. Moreover, berberine reduced the level of tau through an autophagy-based route. It promoted autophagic clearance of tau by enhancing the activity of autophagy via the class III PI3K/beclin-1 pathway. Thus, our results suggest that berberine could mitigate cognitive decline by simultaneously targeting the hyperphosphorylation of tau and the autophagic clearance of tau in AD mice. These findings strongly support berberine as a potential drug candidate for AD.
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