Histone deacetylase 6 (HDAC6) is a key therapeutic target in neurodegenerative diseases such as Alzheimer’s disease (AD), which has been demonstrated to play an essential role in memory function and microtubule-associated tau physiology. In this study, was used to treat AD model rats induced by Aβ/Cu to study the improving effect of on learning and memory impairment in AD rats and its related mechanism, to provide the basis for the subsequent development of as an anti-AD drug. Results showed that could decrease the expression of Aβ, Tau, and p-Tau proteins in the hippocampus of AD rats to inhibit the formation of senile plaques and neurofibrillary tangles, down-regulate the expression of Bax mRNA and Caspase-3 mRNA, and up-regulate the expression of Bcl-2 mRNA to reduce the apoptosis of neuron cells, reverse the expression of TNF-α, IL-1β and IL-6 mRNA to regulate neuroinflammatory response in AD rat brain. also could regulate the oxidative stress state of AD rats, and balance the neurotransmitter disorder in AD rats' brain tissue. Overall, could recover the morphology of hippocampal neurons and improve the learning and memory dysfunction in AD rats by regulating multiple targets in AD rats, providing a promising therapeutic avenue for the treatment of AD.

中文翻译：

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新型HDAC6抑制剂W5对Aβ/Cu2+诱导的阿尔茨海默病模型大鼠的多靶点作用研究

组蛋白脱乙酰酶 6 (HDAC6) 是阿尔茨海默病 (AD) 等神经退行性疾病的关键治疗靶点，已被证明在记忆功能和微管相关 tau 生理学中发挥重要作用。本研究采用Aβ/Cu诱导的AD模型大鼠进行治疗，研究其对AD大鼠学习记忆障碍的改善作用及其相关机制，为后续开发抗AD药物提供依据。结果表明，可降低AD大鼠海马Aβ、Tau、p-Tau蛋白的表达，抑制老年斑和神经原纤维缠结的形成，下调Bax mRNA和Caspase-3 mRNA的表达，上调Bax mRNA和Caspase-3 mRNA的表达。 -调节Bcl-2 mRNA的表达，减少神经元细胞的凋亡，逆转TNF-α、IL-1β和IL-6 mRNA的表达，调节AD大鼠脑内的神经炎症反应。还可以调节AD大鼠的氧化应激状态，平衡AD大鼠脑组织中神经递质的紊乱。总体而言，通过调节AD大鼠的多个靶点，可以恢复AD大鼠海马神经元的形态，改善AD大鼠的学习记忆功能障碍，为AD的治疗提供了一条有前景的治疗途径。