后临床神经元没有活跃的细胞周期。然而，在这些神经元中对细胞周期蛋白依赖性激酶-5（CDK5）活性的放松能量可以使细胞周期的各种组分产生导致神经元死亡（嫦娥.2012）。已显示细胞周期蛋白的随机激活在几种神经变性障碍的发病机制中发挥关键作用（Yang等人，2003年，Lopes等，2009）。CDK5未被规范的阴茎激活，但与其特定的合作伙伴，CDK5R1和CDK5R2（分别为AKA P35和P39）结合（Tsai等，1994，Tang等，1995）。P35的表达几乎普遍存在，而P39在很大程度上在中枢神经系统中表达。各种神经毒性损伤如β-淀粉样（a-β），缺血，促进毒性和氧化胁迫破坏了神经元细胞内钙稳态，从而导致钙骨的活化，将P35切入P25和P10（Lee等人。2000）。与P35相比，P25具有六倍较长的半衰期，并且缺乏膜锚定信号，这导致其CDK5：P25复合物与细胞质和核的组成型激活和错误分析。在那里，CDK5：P25能够进入和磷酸化各种非典型靶标，触发级联的神经毒性途径，这些途径达到神经元死亡。一种这样的神经毒性途径涉及CDK5介导的细胞周期蛋白的随机活化，其达到神经元死亡。 Exposure of primary cortical neurons to oligomeric beta-amyloid (1-42) hyper-activates CDK5 due to p25 formation, which in turn phosphorylates CDC25A, CDC25B and CDC25C. CDK5 phosphorylates CDC25A at S40, S116 and S261; CDC25B at S50, T69, S160, S321 and S470; and CDC25C at T48, T67, S122, T130, S168 and S214. CDK5-mediated phosphorylation of CDC25A, CDC25B and CDC25C not only increases their phosphatase activities but also facilitates their release from 14-3-3 inhibitory binding. CDC25A, CDC25B and CDC25C in turn activate CDK1, CDK2 and CDK4 kinases causing neuronal death. Consistent with this mechanism, higher CDC25A, CDC25B and CDC25C activities were observed in human Alzheimer's disease (AD) clinical samples, as compared to age-matched controls. Inhibition of CDC25 isoforms confers neuroprotection to beta-amyloid toxicity, which underscores the contribution of this pathway to AD pathogenesis