New approaches to treating Alzheimer's disease.
New approaches to treating Alzheimer's disease.
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DOI：
10.4137/pmc.s13210
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Youdim M
中科院分区：
文献类型：
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作者：
Zheng H;Fridkin M;Youdim M
迄今为止，还没有开发出真正有效的治疗阿尔茨海默病（AD）的药物；而且，自2003年以来开发的所有新的抗AD药物都失败了。为了在以前的药物开发失败的领域取得成功，需要新的 AD 治疗方法。在这里，我们讨论网络医学作为 AD 治疗新方法的潜在应用。与专注于单一靶点/途径的传统方法不同，网络医学通过同时调节参与 AD 发病机制的众多蛋白质（靶点）/途径来瞄准并恢复疾病破坏的网络。我们考虑了几种正在开发的 AD 治疗候选药物，包括 Keap1-Nrf2 调节剂、内源性神经源性药物和缺氧诱导因子 1 (HIF-1) 激活剂。这些候选药物是多靶点配体，有可能进一步开发为网络药物，因为它们充当主调节因子来启动广泛的细胞防御机制/细胞保护基因，从而以整体方式发挥其功效。我们还探索了它们的不同作用机制和潜在的疾病缓解作用，这可能对药物发现产生深远的影响。
To date, no truly efficacious drugs for Alzheimer’s disease (AD) have been developed; moreover, all new anti-AD drugs developed since 2003 have failed. To succeed where previous ones have failed in drug development, new approaches for AD therapy are needed. Here we discuss the potential application of network medicine as a new approach to AD treatment. Unlike traditional approaches focused on a single target/pathway, network medicine targets and restores disease-disrupted networks through simultaneous modulation of numerous proteins (targets)/pathways involved in AD pathogenesis. We consider several drug candidates under development for AD therapy, including Keap1–Nrf2 regulators, endogenous neurogenic agents, and hypoxia-inducible factor 1 (HIF-1) activators. These drug candidates are multi-target ligands with the potential to further develop as network medicines, since they act as master regulators to initiate a broad range of cellular defense mechanisms/cytoprotective genes that exert their efficacy in a holistic way. We also explore their diverse mechanisms of action and potential disease-modifying effects, which may have profound implications for drug discovery.