Institute of Molecular Regenerative Medicine, Spinal Cord Injury and Tissue Regeneration Center, Salzburg, Paracelsus Medical University, Salzburg, Austria.
Institute of Molecular Regenerative Medicine, Spinal Cord Injury and Tissue Regeneration Center, Salzburg, Paracelsus Medical University, Salzburg, Austria; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Drug Discov Today. 2019 Feb;24(2):505-516. doi: 10.1016/j.drudis.2018.09.008. Epub 2018 Sep 18.
The underlying pathology of Alzheimer's disease (AD) is complex and includes, besides amyloid beta (Aβ) plaque depositions and neurofibrillary tangles, brain atrophy and neurodegeneration, neuroinflammation, impaired neurogenesis, vascular and blood-brain barrier (BBB) disruptions, neurotransmitter disbalances, and others. Here, we hypothesize that such complex pathologies can only be targeted efficiently through pleiotropic approaches. One interesting drug target is the leukotriene pathway, which mediates various aspects of AD pathology. Approaching this pathway at different levels with genetic and pharmacological tools demonstrated beneficial outcomes in several in vivo studies using different mouse models of AD. Here, we review the current literature on the leukotriene signaling pathway as a target for drug development in AD.
阿尔茨海默病（AD）的潜在病理学较为复杂，除了淀粉样β（Aβ）斑块沉积和神经原纤维缠结外，还包括脑萎缩和神经退行性变、神经炎症、神经发生受损、血管和血脑屏障（BBB）破坏、神经递质失衡等。在这里，我们假设只有通过多效性方法才能有效地靶向这些复杂的病理学。一个有趣的药物靶点是白三烯途径，它介导 AD 病理学的各个方面。使用不同的 AD 小鼠模型，通过遗传和药理学工具在不同水平上靶向该途径，在几项体内研究中均显示出有益的结果。在这里，我们综述了白三烯信号通路作为 AD 药物开发靶点的最新文献。
