Abdulmajeed G. Almutary , M. Yasmin Begum , Ashish Kumar Kyada , Saurabh Gupta , S. Renuka Jyothi , Kamlesh Chaudhary , Swati Sharma , Aashna Sinha , Mosleh Mohammad Abomughaid , Mohd Imran , Sorabh Lakhanpal , Ahmad O. Babalghith , Eman Adnan Abu-Seer , D. Avinash , Hassan A. Alzahrani , Abdulghani A. Alhindi , Danish Iqbal , Sandeep Kumar , Niraj Kumar Jha , Saad Alghamdi
{"title":"Inflammatory signaling pathways in Alzheimer's disease: Mechanistic insights and possible therapeutic interventions","authors":"Abdulmajeed G. Almutary , M. Yasmin Begum , Ashish Kumar Kyada , Saurabh Gupta , S. Renuka Jyothi , Kamlesh Chaudhary , Swati Sharma , Aashna Sinha , Mosleh Mohammad Abomughaid , Mohd Imran , Sorabh Lakhanpal , Ahmad O. Babalghith , Eman Adnan Abu-Seer , D. Avinash , Hassan A. Alzahrani , Abdulghani A. Alhindi , Danish Iqbal , Sandeep Kumar , Niraj Kumar Jha , Saad Alghamdi","doi":"10.1016/j.arr.2024.102548","DOIUrl":null,"url":null,"abstract":"<div><div>The complex pathophysiology of Alzheimer's disease (AD) poses challenges for the development of therapies. Recently, neuroinflammation has been identified as a key pathogenic mechanism underlying AD, while inflammation has emerged as a possible target for the management and prevention of AD. Several prior studies have demonstrated that medications modulating neuroinflammation might lessen AD symptoms, mostly by controlling neuroinflammatory signaling pathways such as the NF-κB, MAPK, NLRP3, etc, and their respective signaling cascade. Moreover, targeting these inflammatory modalities with inhibitors, natural products, and metabolites has been the subject of intensive research because of their anti-inflammatory characteristics, with many studies demonstrating noteworthy pharmacological capabilities and potential clinical applications. Therefore, targeting inflammation is considered a promising strategy for treating AD. This review comprehensively elucidates the neuroinflammatory mechanisms underlying AD progression and the beneficial effects of inhibitors, natural products, and metabolites in AD treatment.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"104 ","pages":"Article 102548"},"PeriodicalIF":12.5000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Ageing Research Reviews","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1568163724003660","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The complex pathophysiology of Alzheimer's disease (AD) poses challenges for the development of therapies. Recently, neuroinflammation has been identified as a key pathogenic mechanism underlying AD, while inflammation has emerged as a possible target for the management and prevention of AD. Several prior studies have demonstrated that medications modulating neuroinflammation might lessen AD symptoms, mostly by controlling neuroinflammatory signaling pathways such as the NF-κB, MAPK, NLRP3, etc, and their respective signaling cascade. Moreover, targeting these inflammatory modalities with inhibitors, natural products, and metabolites has been the subject of intensive research because of their anti-inflammatory characteristics, with many studies demonstrating noteworthy pharmacological capabilities and potential clinical applications. Therefore, targeting inflammation is considered a promising strategy for treating AD. This review comprehensively elucidates the neuroinflammatory mechanisms underlying AD progression and the beneficial effects of inhibitors, natural products, and metabolites in AD treatment.
阿尔茨海默病(AD)是全球常见的痴呆症,是一种包括神经变性在内的复杂疾病,其发病机制尚不完全清楚。信号转导和生物活动(包括细胞代谢、生长和死亡)受不同信号通路的调控,包括 AKT/MAPK、Wnt、Leptin、mTOR、泛素、Sirt1 和胰岛素。目前仍缺乏将特定分子通路与注意力缺失症的发生和/或发展联系起来的绝对证据。肠道微生物群和血脑屏障的变化也会导致 AD 中淀粉样蛋白 β 的聚集。本综述报告了各种信号通路的重要特征、它们之间的关系,以及它们在疾病发生和/或发展过程中如何相互作用。然而,由于大脑的巨大复杂性和这些通路之间的众多化学联系,将信号通路作为药物开发的可能靶点来治疗 AD 的研究少之又少。目前,AD 还没有永久性的治疗方法,也没有办法阻止脑细胞的丢失。本综述还旨在提请人们注意一组新型信号通路(可统称为 "抗 AD 通路")在多靶点治疗 AD(细胞代谢功能严重受损)中的作用。因此,人们提出并阐述了不同的假说来解释 AD 的成因,这些假说也可进一步用于药物开发。
期刊介绍:
With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends.
ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research.
The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.