通过脂联素受体激动剂实现神经保护：阿尔茨海默病临床前研究的最新荟萃分析。

Neuroprotection through adiponectin receptor agonist: an updated meta-analysis of preclinical Alzheimer's disease studies.

作者信息

Novinbahador Tannaz, Abbasi Amin, Molani-Gol Roghayeh, Aghebati-Maleki Leili, Pouraghaei Amirhesam, Soleimanpour Hassan

机构信息

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Emergency and trauma care research center, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

BMC Neurol. 2025 Aug 4;25(1):320. doi: 10.1186/s12883-025-04356-5.

DOI:10.1186/s12883-025-04356-5

PMID:40759907

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12323088/

Abstract

BACKGROUND

Alzheimer’s disease (AD) is a leading cause of dementia, imposing a substantial burden on individuals and society. While existing therapies can reduce the symptoms of AD, they do not offer genuine therapeutic effectiveness. Adiponectin Receptor Agonist (ADN-R Ag) has been proposed as a novel therapeutic agent for AD. This study aims to evaluate its efficacy in treating AD model mice.

METHODS

A systematic search of PubMed, Scopus, Cochrane Library, and Web of Science was conducted up to May 3, 2025. Research investigating the impact of ADN-R Ag on cognitive performance and associated molecular pathways in Alzheimer’s disease models, specifically APP/PS1, P301S, and 5XFAD mice, was incorporated. The Alzheimer’s disease models in the study were male and ranged in age from 5.5 to 8 months. Studies evaluating the effect of ADN-R Ag on AD model mice through cognitive function tests and related molecular mechanisms were included. Methodological quality assessment was performed using the CAMARADES tool for animal studies. The meta-analysis was performed following Cochrane guidelines.

RESULTS

Six articles were included for the review. ADN-R Ag significantly improved cognitive function in the meta-analysis. The weighted mean difference of ADN-R Ag was 21.75 (95% CI: 16.61–26.88; < 0.001) for alternation rate percentage in the Y-maze, 20.46 (95% CI: 11.41–29.51, < 0.001) for novel object exploration time percentage in the novel object recognition (NOR) test, -15.83 (95% CI: -23.33 to -8.32, < 0.001) for escape latency in the Morris water maze (MWM), and 13.89 (95% CI: 8.84–18.94; < 0.001) for target quadrant time in the probe test. Additionally, ADN-R Ag was reported to mitigate AD pathology by reducing Aβ depositions through inhibition of GSK3β/BACE1/NF-κB pathway, suppressing neuronal inflammation by suppressing microglial and astrocytes activity and reducing and IL1β and TNFα levels, enhancing autophagy, and improving mitochondrial function with significant involvement of the AMPK pathway.

CONCLUSION

Based on the current study, ADN-R Ag has therapeutic effects on AD. However, considering the complex underlying molecular mechanisms and limited prior studies, further research is needed.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1186/s12883-025-04356-5.

摘要

背景

阿尔茨海默病（AD）是痴呆症的主要病因，给个人和社会带来了沉重负担。虽然现有疗法可以减轻AD的症状，但它们并未提供真正的治疗效果。脂联素受体激动剂（ADN-R Ag）已被提议作为AD的一种新型治疗药物。本研究旨在评估其治疗AD模型小鼠的疗效。

方法

截至2025年5月3日，对PubMed、Scopus、Cochrane图书馆和Web of Science进行了系统检索。纳入了研究ADN-R Ag对阿尔茨海默病模型（特别是APP/PS1、P301S和5XFAD小鼠）认知性能和相关分子途径影响的研究。研究中的阿尔茨海默病模型为雄性，年龄在5.5至8个月之间。纳入了通过认知功能测试和相关分子机制评估ADN-R Ag对AD模型小鼠影响的研究。使用CAMARADES工具对动物研究进行方法学质量评估。按照Cochrane指南进行荟萃分析。

结果

纳入6篇文章进行综述。在荟萃分析中，ADN-R Ag显著改善了认知功能。在Y迷宫中，ADN-R Ag的加权平均差异为交替率百分比21.75（95%CI：16.61–26.88；P<0.001），在新物体识别（NOR）测试中为新物体探索时间百分比20.46（95%CI：11.41–29.51，P<0.001），在莫里斯水迷宫（MWM）中为逃避潜伏期-15.83（95%CI：-23.33至-8.32，P<0.001），在探针测试中为目标象限时间1,3.89（95%CI：8.84–18.94；P<0.001）。此外，据报道，ADN-R Ag通过抑制GSK3β/BACE1/NF-κB途径减少Aβ沉积、通过抑制小胶质细胞和星形胶质细胞活性以及降低IL1β和TNFα水平来减轻AD病理学、增强自噬并通过AMPK途径的显著参与改善线粒体功能。