Lin Zhongying, Sun Miao
Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, Liaoning, PR China.
Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, PR China.
Pharmacol Res. 2025 Jun;216:107790. doi: 10.1016/j.phrs.2025.107790. Epub 2025 May 21.
Alzheimer's disease (AD) is a common neurodegenerative disorder that leads to cognitive decline. CaMKII is a calcium-regulated kinase that is crucial for synaptic plasticity and memory. Phytochemicals with diverse origins, safety, and biological activity have attracted considerable attention in AD research. This systematic analysis of phytochemicals targeting CaMKII reveals their neuroprotective mechanisms against AD pathogenesis, highlighting CaMKII as a promising therapeutic target that warrants further preclinical investigation and drug development. We conducted a comprehensive review of the literature of phytochemicals that target CaMKII as a protective mechanism against AD. The search was conducted across multiple databases, including PubMed, Web of Science, China National Knowledge Internet, and Google Scholar, and covered the period from January 2000 to October 2024. A total of 301 articles were retrieved, of which 22 articles were included. The results showed that flavonoid, glycoside, terpene, and polyphenol analogs positively regulated CaMKII expression, whereas alkaloid analogs negatively regulated CaMKII expression. Different components of traditional Chinese medicine played different roles in CaMKII expression. Flavonoid compounds upregulated the expression of SYN, PSD-95, MAP2, and GluR1 to exert neuroprotective effects. Alkaloid and glycoside analogs inhibited Aβ deposition and tau hyperphosphorylation. Terpene analogs upregulated the SYN, PSD-95, NMDAR, BDNF, and PI3K/Akt signaling pathways to exert neuroprotection. Polyphenol analogs upregulated PSD-95, Munc18-1, SNAP25, SYN, and BDNF to exert neuroprotective effects. Emerging evidence demonstrates that select phytochemicals and traditional Chinese medicine compounds exert neuroprotective effects in AD by modulating CaMKII activity, thereby reducing Aβ accumulation, attenuating tau hyperphosphorylation, and enhancing synaptic plasticity, suggesting promising therapeutic potential.
阿尔茨海默病（AD）是一种常见的神经退行性疾病，可导致认知功能下降。钙/钙调蛋白依赖性蛋白激酶II（CaMKII）是一种钙调节激酶，对突触可塑性和记忆至关重要。具有多种来源、安全性和生物活性的植物化学物质在AD研究中引起了相当大的关注。这种针对CaMKII的植物化学物质的系统分析揭示了它们针对AD发病机制的神经保护机制，突出了CaMKII作为一个有前景的治疗靶点，值得进一步的临床前研究和药物开发。我们对以CaMKII作为针对AD的保护机制的植物化学物质的文献进行了全面综述。检索在多个数据库中进行，包括PubMed、科学网、中国知网和谷歌学术，涵盖2000年1月至2024年10月期间。共检索到301篇文章，其中纳入22篇。结果表明，黄酮类、糖苷类、萜类和多酚类似物正向调节CaMKII表达，而生物碱类似物负向调节CaMKII表达。中药的不同成分在CaMKII表达中发挥不同作用。黄酮类化合物上调突触蛋白（SYN）、突触后致密蛋白95（PSD-95）、微管相关蛋白2（MAP2）和谷氨酸受体1（GluR1）的表达以发挥神经保护作用。生物碱和糖苷类似物抑制β-淀粉样蛋白（Aβ）沉积和tau蛋白过度磷酸化。萜类类似物上调SYN、PSD-95、N-甲基-D-天冬氨酸受体（NMDAR）、脑源性神经营养因子（BDNF）和磷脂酰肌醇-3-激酶/蛋白激酶B（PI3K/Akt）信号通路以发挥神经保护作用。多酚类似物上调PSD-95、 syntaxin结合蛋白1（Munc18-1）、突触小体相关蛋白25（SNAP25）、SYN和BDNF以发挥神经保护作用。新出现的证据表明，某些植物化学物质和中药化合物通过调节CaMKII活性在AD中发挥神经保护作用，从而减少Aβ积累、减轻tau蛋白过度磷酸化并增强突触可塑性，显示出有前景的治疗潜力。
