Soucek Thomas, Cumming Robert, Dargusch Richard, Maher Pamela, Schubert David
The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Neuron. 2003 Jul 3;39(1):43-56. doi: 10.1016/s0896-6273(03)00367-2.
It is frequently argued that both amyloid beta (Abeta) and oxidative stress are involved in the pathogenesis of Alzheimer's disease (AD). We show here that clonal nerve cell lines and primary cortical neurons that are resistant to Abeta toxicity have an enhanced flux of glucose through both the glycolytic pathway and the hexose monophosphate shunt. AD brain also has increased enzymatic activities in both pathways relative to age-matched controls. The Abeta-induced changes in glucose metabolism are due to the activation of the transcription factor hypoxia inducible factor 1 (HIF-1). As a result of Abeta-induced changes in glucose metabolism, Abeta-resistant cells are more readily killed by glucose starvation and by classes of antipsychotic drugs that inhibit glucose uptake.
人们经常认为，β-淀粉样蛋白（Aβ）和氧化应激都与阿尔茨海默病（AD）的发病机制有关。我们在此表明，对Aβ毒性具有抗性的克隆神经细胞系和原代皮质神经元，通过糖酵解途径和磷酸戊糖途径的葡萄糖通量增加。相对于年龄匹配的对照组，AD脑在这两条途径中的酶活性也有所增加。Aβ诱导的葡萄糖代谢变化是由于转录因子缺氧诱导因子1（HIF-1）的激活。由于Aβ诱导的葡萄糖代谢变化，抗Aβ细胞更容易因葡萄糖饥饿和抑制葡萄糖摄取的抗精神病药物而死亡。
