Alzheimer's disease (AD) is one of the most common neurodegenerative disorders, which is characterized by the primary risk factor, age. Several attempts have been made to treat AD, while most of them end in failure. However, with the deepening study of pathogenesis of AD, the expression of HDAC6 in the hippocampus, which plays a major role of the memory formation, is becoming worth of notice. Neurofibrillary tangles (NFTs), a remarkable lesion in AD, has been characterized in association with the abnormal accumulation of hyperphosphorylated Tau, which is mainly caused by the high expression of HDAC6. On the other hand, the hypoacetylated tubulin induced by HDAC6 is also fatal for the neuronal transport, which is the key impact of the formation of axons and dendrites. Overall, the significantly increased expression of HDAC6 in brain regions is deleterious to neuron survival in AD patients. Based on the above research, the inhibition of HDAC6 seems to be a potential therapeutic method for the treatment of AD. Up to now, various types of HDAC6 inhibitors have been discovered. This review mainly analyzes the HDAC6 inhibitors reported amid 2010–2020 in terms of their structure, selectivity and pharmacological impact towards AD. And we aim at facilitating the design and development of better HDAC6 inhibitors in the future.

阿尔茨海默病 (AD) 是最常见的神经退行性疾病之一，其主要危险因素是年龄。已经进行了几次治疗AD的尝试，但大多数都以失败告终。但随着对AD发病机制研究的深入，对记忆形成起主要作用的HDAC6在海马区的表达越来越值得关注。神经原纤维缠结 (NFTs) 是 AD 中的一种显着病变，其特征与过度磷酸化 Tau 的异常积累有关，这主要是由 HDAC6 的高表达引起的。另一方面，HDAC6 诱导的低乙酰化微管蛋白对神经元运输也是致命的，这是轴突和树突形成的关键影响。全面的，脑区 HDAC6 的表达显着增加对 AD 患者的神经元存活有害。基于上述研究，抑制HDAC6似乎是治疗AD的潜在治疗方法。迄今为止，已经发现了多种类型的HDAC6抑制剂。本综述主要分析了 2010-2020 年间报道的 HDAC6 抑制剂的结构、选择性和对 AD 的药理影响。我们的目标是促进未来更好的 HDAC6 抑制剂的设计和开发。本综述主要分析了 2010-2020 年间报道的 HDAC6 抑制剂的结构、选择性和对 AD 的药理影响。我们的目标是促进未来更好的 HDAC6 抑制剂的设计和开发。本综述主要分析了 2010-2020 年间报道的 HDAC6 抑制剂的结构、选择性和对 AD 的药理影响。我们的目标是促进未来更好的 HDAC6 抑制剂的设计和开发。