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脂联素受体激动剂对阿尔茨海默病的影响——一项系统评价与荟萃分析

AdipoRon's Impact on Alzheimer's Disease-A Systematic Review and Meta-Analysis.

作者信息

Barbalho Sandra Maria, Laurindo Lucas Fornari, de Oliveira Zanuso Bárbara, da Silva Rebeca Maria Siqueira, Gallerani Caglioni Lívia, Nunes Junqueira de Moraes Victor Bruno Fonseca, Fornari Laurindo Lívia, Dogani Rodrigues Victória, da Silva Camarinha Oliveira Jéssica, Beluce Maria Eduarda, Penteado Detregiachi Cláudia Rucco, Barbalho Lamas Caroline, Dos Santos Haber Jesselina Francisco, Cavallari Strozze Catharin Virgínia Maria, Quesada Karina, Tanaka Masaru, Valenti Vitor Engrácia

机构信息

Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil.

Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil.

出版信息

Int J Mol Sci. 2025 Jan 8;26(2):484. doi: 10.3390/ijms26020484.

Abstract

Alzheimer's disease (AD) remains a leading cause of cognitive decline and mortality worldwide, characterized by neurodegeneration, synaptic deficiencies, and neuroinflammation. Despite advancements in early detection, diagnosis, and treatment, AD presents substantial challenges due to its complex pathology, heterogeneity, and the limited efficacy of current therapies. Consequently, there is a pressing need for novel therapeutic agents to target the multifaceted aspects of AD pathology, enhance current treatments, and minimize adverse effects. AdipoRon, an adiponectin receptor agonist, has garnered interest for its potential neuroprotective effects, including reducing neuroinflammation, improving mitochondrial function, and mitigating tau hyperphosphorylation. This review aimed to evaluate the effects of AdipoRon-based adiponectin replacement therapy against AD, using a comprehensive approach grounded in the PICO framework-Population, Intervention, Comparison, and Outcomes. A total of six studies were reviewed, including in vitro and in vivo investigations examining AdipoRon's impact on various AD models. These studies involved different cell lines and transgenic mouse models, assessing various outcomes such as cognitive function, neuroinflammation, tau phosphorylation, synaptic deficiencies, and relevant molecular pathways. By synthesizing data from these studies, our review thoroughly explains AdipoRon's neuroprotective effects, mechanisms of action, and potential as a therapeutic agent for AD. This analysis aims to highlight the current state of knowledge, identify gaps in the research, and suggest directions for future studies and clinical applications.

摘要

阿尔茨海默病(AD)仍然是全球认知功能衰退和死亡的主要原因,其特征为神经退行性变、突触缺陷和神经炎症。尽管在早期检测、诊断和治疗方面取得了进展,但由于其复杂的病理学、异质性以及当前疗法疗效有限,AD仍然面临重大挑战。因此,迫切需要新型治疗药物来针对AD病理学的多方面因素,增强现有治疗效果,并尽量减少不良反应。脂联素受体激动剂AdipoRon因其潜在的神经保护作用而受到关注,包括减轻神经炎症、改善线粒体功能以及减轻tau蛋白过度磷酸化。本综述旨在采用基于PICO框架(人群、干预措施、对照和结局)的综合方法,评估基于AdipoRon的脂联素替代疗法对AD的影响。共综述了六项研究,包括体外和体内研究,考察AdipoRon对各种AD模型的影响。这些研究涉及不同的细胞系和转基因小鼠模型,评估了各种结局,如认知功能、神经炎症、tau蛋白磷酸化、突触缺陷以及相关分子途径。通过综合这些研究的数据,我们的综述全面解释了AdipoRon的神经保护作用、作用机制以及作为AD治疗药物的潜力。本分析旨在突出当前的知识状态,识别研究中的差距,并为未来的研究和临床应用提出方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b8f/11765103/514caff38b68/ijms-26-00484-g001.jpg

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