Berberine Improves Behavioral and Cognitive Deficits in a Mouse Model of Alzheimer's Disease via Regulation of β-Amyloid Production and Endoplasmic Reticulum Stress
Berberine Improves Behavioral and Cognitive Deficits in a Mouse Model of Alzheimer's Disease via Regulation of β-Amyloid Production and Endoplasmic Reticulum Stress
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小檗碱通过调节β-淀粉样蛋白的产生和内质网应激改善阿尔茨海默病小鼠模型的行为和认知缺陷
DOI：
10.1021/acschemneuro.0c00808
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发表时间：
2021-05-13
影响因子：
5
通讯作者：
Huang, Min
中科院分区：
文献类型：
--
作者：
Liang, Yubin;Ye, Chenghui;Huang, Min
Alzheimer's disease (AD) is a neurodegenerative disease characterized by beta-amyloid (A beta), neurofibrillary tangles, and neuronal cell death. Aggressive A beta accumulation accelerates senile plaque formation and perturbs endoplasmic reticulum (ER) function. A beta accumulation-induced changes stimulate the unfolded protein response (UPR), which can trigger neuronal apoptosis. Protein kinase RNA-like endoplasmic reticulum kinase (PERK), whose activation is stress-dependent, increases the phosphorylation of eukaryotic translation initiation factor-2 alpha (eIF2 alpha). eIF2 alpha promotes the synthesis of beta-site APP cleavage enzyme 1 (BACE1), which in turn facilitates A beta generation and subsequent neuronal apoptosis. In this study, we investigated whether berberine could improve cognitive deficits in the triple-transgenic mouse model of Alzheimer's disease (3 x Tg AD) mice. Our results revealed that berberine treatment may inhibit PERK/eIF2 alpha signaling-mediated BACE1 translation, thus reducing A beta production and resultant neuronal apoptosis. Further, berberine may have neuroprotective effects, via attenuation of ER stress and oxidative stress. In sum, our study demonstrates the therapeutic potential of berberine for treating AD.
