扶芝散通过p62和相关的自噬调节途径改善阿尔茨海默病的认知能力。

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research Pub Date : 2024-12-28 DOI:10.1016/j.brainres.2024.149436

Zhaoxu Zhang , Shuangmei Zhang , Shen Liu , Yang He , Anrong Wang

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引用次数: 0

摘要

背景：维持自噬稳态已被证明在阿尔茨海默病中起重要作用。目的：研究扶正散对阿尔茨海默病自噬功能的影响，并通过P62调控途径阐明其潜在机制。方法：采用水提-旋转蒸发法提取FZS。采用新颖物体识别实验、morris水迷宫实验和Y迷宫实验观察APP/PS1小鼠的认知记忆能力。透射电镜观察FZS对小鼠海马超微结构的影响。进一步检测分子水平的变化，包括Aβ沉积、tau过度磷酸化、SOD、CAT和自噬相关蛋白（p62、Nrf2、keap1、mTOR、LC3II/I、Beclin1、Atgs）。结果：FZS可减轻APP/PS1小鼠的记忆和认知功能障碍，增加海马自噬囊泡和细胞器的丰度。FZS还能降低模型小鼠海马Aβ和tau过度磷酸化水平，上调SOD、CAT和自噬相关蛋白（Nrf2、LC3II/LC3I、Beclin1、Atg7和Atg12）水平，下调P62、keap1和p-mTOR/mTOR蛋白的表达。Co-Ip结果显示，FZS提高了p62/LC3和p62 -keap1- nrf2复合物的水平，但降低了p62和keap1的关联。结论：我们的研究结果表明，FZS可能通过调节P62及相关通路，促进a β和磷酸化tau的清除，从而影响自噬功能和氧化应激，从而提高AD的认知能力，为探索FZS治疗AD的潜在机制提供了新的视角。

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Fuzhisan ameliorates cognitive ability in Alzheimer’s disease by p62 and related autophagy regulatory pathways

Background

Maintaining autophagic homeostasis has been proved to play an important role in Alzheimer’s disease.

Object

The aim of this study was to investigate the effect of Fuzhisan(FZS) on autophagic function in Alzheimer’s disease and to elucidate its potential mechanism through the P62 regulatory pathways.

Methods

FZS was extracted by water extraction-rotary evaporation method. The novel object recognition test, morris water maze test and Y maze test were used to observe the cognitive and memory ability of APP/PS1 mice. The effects of FZS on the ultrastructure of mice hippocampus were examined by transmission electron microscopy. Molecular level changes were also further detected, including Aβ deposition, tau hyperphosphorylation, SOD, CAT and autophagy related proteins (p62, Nrf2, keap1, mTOR, LC3II/I, Beclin1, Atgs).

Results

FZS could alleviate memory and cognitive impairment in APP/PS1 mice, increase the autophagic vesicles and organelle abundance in hippocampus. FZS also reduced the levels of Aβ and tau hyperphosphorylation in the hippocampus of model mice, upregulated the levels of SOD, CAT and autophagy related proteins (Nrf2, LC3II/LC3I, Beclin1, Atg7 and Atg12) as well as downregulated the expression of P62, keap1 and p-mTOR/mTOR proteins. Co-Ip results showed that FZS elevated the levels of p62/LC3 and P62-keap1-Nrf2 complex, but decreased the P62 and keap1 association.

Conclusion

Our findings indicate that FZS may affect autophagy function and oxidative stress by regulating P62 and related pathways to promote the clearance of Aβ and phosphorylated tau, thereby improving the cognitive ability of AD, which provided a novel perspective for exploring the potential mechanism of FZS upon AD.

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来源期刊

Brain Research 医学-神经科学

CiteScore

5.90

自引率

3.40%

发文量

268

审稿时长

47 days

期刊介绍： An international multidisciplinary journal devoted to fundamental research in the brain sciences. Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed. With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.