Berberine mitigates cognitive decline in an Alzheimer's Disease Mouse Model by targeting both tau hyperphosphorylation and autophagic clearance
Berberine mitigates cognitive decline in an Alzheimer's Disease Mouse Model by targeting both tau hyperphosphorylation and autophagic clearance
复制标题
小檗碱通过靶向 tau 过度磷酸化和自噬清除来减轻阿尔茨海默病小鼠模型的认知能力下降
DOI：
10.1016/j.biopha.2019.109670
复制
发表时间：
2020-01-01
影响因子：
7.5
通讯作者：
Huang, Min
中科院分区：
文献类型：
--
作者：
Chen, Ying;Chen, Yuling;Huang, Min
小檗碱是从黄连中分离出来的天然异喹啉类生物碱。最近的研究进展更多地揭示了其对阿尔茨海默病（AD）的有益作用，包括促进β -淀粉样蛋白（A β）的清除，以及抑制阿尔茨海默病（3xTg AD）三重转基因小鼠模型中A β的产生。然而，小檗碱是否对tau病理有影响尚不清楚。根据我们的研究，小檗碱不仅能显著提高3xTg AD小鼠的空间学习能力和记忆保留能力，还能减弱tau蛋白的过度磷酸化。通过调节Akt/糖原合成酶激酶-3 β和蛋白磷酸酶2A的活性。此外，小檗碱通过基于自噬的途径降低了tau的水平。它通过III类PI3K/beclin-1途径增强自噬活性，促进tau的自噬清除。因此，我们的研究结果表明，小檗碱可以同时靶向AD小鼠tau蛋白的过度磷酸化和tau蛋白的自噬清除，从而减轻认知能力下降。这些发现有力地支持了小檗碱作为阿尔茨海默病的潜在候选药物。
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.