Acupuncture Research Center, Tianjin University of Traditional Chinese Medicine, Tianjin, China
Acu-moxibustion and Tuina Department, Tianjin University of Traditional Chinese Medicine, Tianjin, China
Curr Pharm Des. 2020;26(39):5054-5066. doi: 10.2174/1381612826666200523172334.
Neurodegenerative disorders are heterogeneous diseases associated with either acute or progressive neurodegeneration, causing the loss of neurons and axons in the central nervous system (CNS), showing high morbidity and mortality, and there are only a few effective therapies. Here, we summarized that the energy sensor adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), and its agonist berberine can combat the common underlying pathological events of neurodegeneration, including oxidative stress, neuroinflammation, mitochondrial disorder, glutamate excitotoxicity, apoptosis, autophagy disorder, and disruption of neurovascular units. The abovementioned effects of berberine may primarily depend on activating AMPK and its downstream targets, such as the mammalian target of rapamycin (mTOR), sirtuin1 (SIRT1), nuclear factor erythroid-2 related factor-2 (Nrf2), nuclear factor-κB (NF-κB), phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), nicotinamide adenine dinucleotide (NAD+), and p38 mitogen-activated protein kinase (p38 MAPK). It is hoped that this review will provide a strong basis for further scientific exploration and development of berberine's therapeutic potential against neurodegeneration.
神经退行性疾病是与中枢神经系统（CNS）中的急性或进行性神经退行性变相关的异质性疾病，导致神经元和轴突丧失，具有高发病率和死亡率，目前仅有少数有效治疗方法。在这里，我们总结了能量传感器腺苷 5'-单磷酸（AMP）激活的蛋白激酶（AMPK）及其激动剂小檗碱可以对抗神经退行性变的常见潜在病理事件，包括氧化应激、神经炎症、线粒体障碍、谷氨酸兴奋性毒性、细胞凋亡、自噬障碍和神经血管单元的破坏。小檗碱的上述作用可能主要取决于激活 AMPK 及其下游靶点，如雷帕霉素（mTOR）的哺乳动物靶标、沉默调节蛋白 1（SIRT1）、核因子红细胞 2 相关因子 2（Nrf2）、核因子-κB（NF-κB）、磷酸肌醇 3-激酶/蛋白激酶 B（PI3K/Akt）、烟酰胺腺嘌呤二核苷酸（NAD+）和 p38 丝裂原活化蛋白激酶（p38 MAPK）。希望本综述为进一步探索和开发小檗碱治疗神经退行性疾病的潜力提供坚实的科学依据。
