通过干扰PSD-95与nr2b亚型受体的相互作用，tata - nr2b9c可预防Aβ1-42诱导的阿尔茨海默病模型小鼠的认知功能障碍

IF 2.9 Q3 NEUROSCIENCES

IBRO Neuroscience Reports Pub Date : 2025-07-19 DOI:10.1016/j.ibneur.2025.07.006

Yaqin Huang, Weiping Lei, Jiahong Shen, Jianliang Sun

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引用次数: 0

摘要

阿尔茨海默病（AD）是一种常见的进行性和致死性神经退行性疾病，其主要临床症状为进行性记忆障碍和认知功能障碍。Tat-NR2B9c是一种被称为突触后密度蛋白-95（PSD-95）抑制剂的肽，在一些疾病如急性中风和神经性疼痛中显示出神经保护作用的临床疗效。这项研究的目的是阐明Tat-NR2B9c是否对阿尔茨海默病具有相同的神经保护作用。方法采用a - β1 - 42诱导小鼠AD模型。模拟AD后给予药物治疗14 d，评估药物治疗后大鼠空间学习记忆能力。然后，对小鼠实施安乐死，进行生化测试。结果AD小鼠海马PSD-95、NR2B水平降低，n-甲基-d-天冬氨酸受体-突触后密度蛋白-95相互作用水平升高。塔特- nr2b9c可通过干扰PSD-95与nr2b亚型的相互作用改善AD小鼠的空间学习记忆能力，但不抑制PSD-95水平。结论tata - nr2b9c可通过干扰PSD-95与nr2b亚型受体的相互作用，预防Aβ1-42诱导的AD模型小鼠认知功能障碍。

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Tat-NR2B9c prevent cognitive dysfunction in mice modeling Alzheimer's Disease induced by Aβ1–42 via perturbing PSD-95 interactions with NR2B-subtype receptors

Background

Alzheimer’s Disease (AD) is one of common progressive and fatal neurodegenerative disorders,and its main clinical symptoms are progressive memory impairment and cognitive dysfunction. The Tat-NR2B9c, a peptide was known as postsynaptic density protein-95(PSD-95) inhibitors, has shown clinical efficacy as a neuroprotective effects in some diseases such as acute stroke and neuropathic pain.

The aim of the study is to clarify whether Tat-NR2B9c has the same neuroprotective effects in AD.

Methods

Studies were performed in mice modeling AD induced by Aβ_1–42. Animals were treated with drugs after modeling AD for 14 days,and the spatial learning and memory ability were assessed after drug treatment. Then, mice were euthanized for biochemical tests.

Results

The levels of PSD-95 and NR2B decreased,and the levels of N-methyl-d-aspartate receptor–postsynaptic density protein-95 interaction increased in hippocampus in AD mice. Tat-NR2B9c can improve spatial learning and memory ability in AD mice by perturbing PSD-95 interactions with NR2B-subtype but not inhibiting PSD-95 levels.