Department of Neurology, First Affiliated Hospital, Harbin Medical University, 150001 Harbin, China.
Neurochem Res. 2011 May;36(5):801-11. doi: 10.1007/s11064-011-0405-6. Epub 2011 Jan 18.
It has been shown that β-amyloid (Aβ) induced hyperphosphorylation of tau is implicated in the pathogenesis of Alzheimer's disease (AD), and deregulation of cyclin-dependent kinase 5 (Cdk5) activity is involved in the abnormal tau phosphorylation. The cleavage of neuron-specific Cdk5 activator, p35, to p25, mediated by calpain and calcium, deregulates Cdk5 activity and promotes neurodegeneration. Fuzhisan (FZS), a Chinese herbal complex prescription that has been used for the treatment of AD for over 15 years, is known to enhance the cognitive ability in AD patients. In this study, we investigated the neuroprotective effects and potential molecular mechanisms of FZS against Aβ(25-35)-induced toxicity in cultured cortical neurons. We revealed that FZS attenuated Aβ(25-35)-induced neurotoxicity in a dose-dependent manner. FZS inhibited Aβ(25-35)-induced activation of Cdk5 and decreased tau hyperphosphorylation although it did not directly inhibit Cdk5. In addition, FZS also blocked Aβ(25-35)-induced calcium influx, calpain activation and decreased cleavage of p35 to p25.
已有研究表明，β-淀粉样蛋白（Aβ）诱导的 tau 过度磷酸化与阿尔茨海默病（AD）的发病机制有关，细胞周期蛋白依赖性激酶 5（Cdk5）活性的失调与 tau 的异常磷酸化有关。钙蛋白酶和钙介导的神经元特异性 Cdk5 激活剂 p35 切割为 p25，会导致 Cdk5 活性失调，促进神经退行性变。复智散（FZS）是一种中药复方处方，已用于治疗 AD 超过 15 年，已知可增强 AD 患者的认知能力。在这项研究中，我们研究了 FZS 对培养的皮质神经元中 Aβ（25-35）诱导的毒性的神经保护作用及其潜在的分子机制。结果表明，FZS 以剂量依赖的方式减弱 Aβ（25-35）诱导的神经毒性。FZS 抑制 Aβ（25-35）诱导的 Cdk5 激活，并降低 tau 过度磷酸化，尽管它不能直接抑制 Cdk5。此外，FZS 还阻断 Aβ（25-35）诱导的钙内流、钙蛋白酶激活和 p35 向 p25 的切割。
