Zinc-dependent deacetylases (HDACs) as potential targets for treating Alzheimer's disease
Zinc-dependent deacetylases (HDACs) as potential targets for treating Alzheimer's disease
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DOI：
10.1016/j.bmcl.2022.129015
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发表时间：
2022-10-07
影响因子：
2.7
通讯作者：
He, Bin
中科院分区：
文献类型：
--
作者：
Li, Yan;Lin, Shuxian;He, Bin
阿尔茨海默病(AD)作为最常见的痴呆类型，已成为全球老年人健康和生命的最大威胁之一。虽然人们在抗AD药物的发现上做了很大的努力，但这些批准的药物只是暂时缓解了症状，并没有完全阻止神经病理的进展。开发针对其他治疗靶点的更有效的药物是非常迫切和合理的。在过去的二十年里，锌依赖的脱乙酰酶(HDAC)作为一组重要的表观遗传学靶点在药物开发中引起了人们的极大关注，因为已经有五种HDAC抑制剂被批准用于临床治疗癌症。本文就HDACs在AD病理生理学中的可能作用及其抑制剂在AD研究中的应用作一综述。并对HDAC作为表观遗传靶点通过其选择性抑制剂、多靶点抑制剂或PROTAC治疗AD的未来前景进行了讨论。
Alzheimer's disease (AD) as the most prevalent dementia type has become one of the greatest threats to the health and life of the elder people worldwide. Although there has been a great effort in the discovery of anti-AD drugs, those approval drugs only demonstrated the temporarily relieving the symptoms without completely stopping the progression of the neuropathology. It is very urgent and reasonable to develop more effective agents against other therapeutic targets. In the last two decades, zinc-dependent deacetylases (HDACs) have attracted much attention as an important group of epigenetic targets in drug discovery, because five HDAC inhibitors have been approved for clinically treating cancers. This review is to summarize the possible roles of HDACs in AD pathophysiology and their inhibitors used in AD studies. And the future perspectives related to HDACs as epigenetic targets for treating AD by their selective inhibitors, multi-target inhibitors or PROTACs are also discussed.