Department of Pharmacology and Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA, USA.
J Alzheimers Dis. 2014;38(3):503-6. doi: 10.3233/JAD-131223.
Inflammatory mechanisms have been implicated in Alzheimer's disease (AD) pathogenesis, and among them, the pro-inflammatory 5-lipoxygenase (5LO) enzyme. While previous work has shown that 5LO modulates the amyloidotic phenotype of AD, the exact metabolic product responsible for this biological action remains unknown. In this study, we challenged neuronal cells with leukotriene B4 (LTB4), a major 5LO product, and found that it increased amyloid-β formation whereby elevating the steady-state levels of the γ-secretase proteins, suggesting that LTB4 is the mediator of the 5LO effect. Therapies that by blocking 5LO activation suppress the formation of LTB4 or its action represent novel AD therapeutic opportunities.
炎症机制被认为与阿尔茨海默病（AD）的发病机制有关，其中包括促炎的 5-脂氧合酶（5LO）。虽然之前的研究表明 5LO 调节 AD 的淀粉样表型，但负责这种生物学作用的确切代谢产物仍不清楚。在这项研究中，我们用白三烯 B4（LTB4）刺激神经元细胞，LTB4 是 5LO 的主要产物之一，结果发现它增加了淀粉样-β的形成，从而提高了 γ-分泌酶蛋白的稳定水平，这表明 LTB4 是 5LO 作用的介导物。通过阻断 5LO 激活来抑制 LTB4 的形成或其作用的治疗方法代表了新的 AD 治疗机会。
