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海马齿状回区域中USP9X的下调导致小鼠出现类似阿尔茨海默病的认知功能障碍。

Downregulation of USP9X in the DG Region of the Hippocampus Leads to AD-Like Cognitive Dysfunction in Mice.

作者信息

Qi Xiaochuan, Ying Mengjiao, Wang Ao, Shi Kelin, Zhong Guangshang, Lu Yichao, Liu Changqing, Guo Yu

机构信息

Anhui Engineering Research Centre for Neural Regeneration Technology and Medical New Materials, Bengbu Medical University, Bengbu, China.

School of Laboratory Medicine, Bengbu Medical University, Bengbu, China.

出版信息

CNS Neurosci Ther. 2025 Jul;31(7):e70493. doi: 10.1111/cns.70493.

DOI:10.1111/cns.70493
PMID:40586131
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12207322/
Abstract

OBJECTIVE

This study investigates the link between ubiquitin-specific peptidase 9 X-linked (USP9X) and Alzheimer's disease (AD) pathogenesis, aiming to identify potential targets for AD diagnosis, treatment, and drug development.

METHODS

We constructed a USP9X-inhibited expression mouse model and assessed cognitive and memory functions. We also measured Tau phosphorylation and APP levels in the hippocampal dentate gyrus (DG) and analyzed neuronal functions, dendritic spine features, late apoptosis, and autophagy.

RESULTS

Mice with USP9Xinhibition exhibited impaired cognitive and memory functions. An increase in the APP levels and Tau hyperphosphorylation in the DG resembled AD-like pathology. Neurons exhibited abnormal functions, altered dendritic spine morphology, increase in neuronal apoptosis, and dysfunctions, similar to neuron loss observed in AD.

CONCLUSION

Investigating the role of USP9X in AD could provide valuable insights for developing novel diagnostic and therapeutic strategies for AD.

摘要

目的

本研究调查泛素特异性肽酶9 X连锁（USP9X）与阿尔茨海默病（AD）发病机制之间的联系，旨在确定AD诊断、治疗和药物开发的潜在靶点。

方法

我们构建了USP9X抑制表达小鼠模型，并评估认知和记忆功能。我们还测量了海马齿状回（DG）中Tau蛋白磷酸化和APP水平，并分析了神经元功能、树突棘特征、晚期凋亡和自噬。

结果

USP9X抑制的小鼠表现出认知和记忆功能受损。DG中APP水平升高和Tau蛋白过度磷酸化类似于AD样病理。神经元表现出异常功能、树突棘形态改变、神经元凋亡增加和功能障碍，类似于AD中观察到的神经元丢失。

结论

研究USP9X在AD中的作用可为开发AD的新型诊断和治疗策略提供有价值的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61bf/12207322/e152d72649cf/CNS-31-e70493-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61bf/12207322/10867c7baa2f/CNS-31-e70493-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61bf/12207322/d9935bdfb6b0/CNS-31-e70493-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61bf/12207322/1fb79a3fcbfb/CNS-31-e70493-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61bf/12207322/432f0c71ad05/CNS-31-e70493-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61bf/12207322/e152d72649cf/CNS-31-e70493-g002.jpg

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本文引用的文献

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