Huang Yaqin, Lei Weiping, Shen Jiahong, Sun Jianliang
Department of Anesthesia, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou 310006, China.
IBRO Neurosci Rep. 2025 Jul 19;19:317-322. doi: 10.1016/j.ibneur.2025.07.006. eCollection 2025 Dec.
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.
Studies were performed in mice modeling AD induced by Aβ. 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.
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.
Tat-NR2B9c can prevent cognitive dysfunction in mice modeling AD induced by Aβ1-42 via perturbing PSD-95 interactions with NR2B-subtype receptors.
阿尔茨海默病（AD）是常见的进行性致命神经退行性疾病之一，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致密蛋白95（PSD-95）抑制剂的肽，在急性中风和神经性疼痛等一些疾病中已显示出作为神经保护作用的临床疗效。本研究的目的是阐明Tat-NR2B9c在AD中是否具有相同的神经保护作用。
在由Aβ诱导的AD小鼠模型中进行研究。在建立AD模型14天后用药物治疗动物，并在药物治疗后评估其空间学习和记忆能力。然后，对小鼠实施安乐死以进行生化检测。
AD小鼠海马中PSD-95和NR2B水平降低，N-甲基-D-天冬氨酸受体-突触后致密蛋白95相互作用水平升高。Tat-NR2B9c可通过干扰PSD-95与NR2B亚型的相互作用而非抑制PSD-95水平来改善AD小鼠的空间学习和记忆能力。
Tat-NR2B9c可通过干扰PSD-95与NR2B亚型受体的相互作用来预防由Aβ1-42诱导的AD小鼠模型中的认知功能障碍。
