{"title":"阿尔茨海默病中的自由基:从病理生理学到临床试验结果。","authors":"José Viña, Consuelo Borrás, Cristina Mas-Bargues","doi":"10.1016/j.freeradbiomed.2024.09.051","DOIUrl":null,"url":null,"abstract":"<p><p>In this review, we examine the role of oxidative stress in the pathophysiology of Alzheimer's Disease (AD). Amyloid-beta (Aβ) induces damage not only extracellularly but also within the intracellular environment. Mitochondria, a principal source of free radicals, are closely associated with Aβ, as it binds to heme, thereby disrupting the normal electron flow in the respiratory chain. At the turn of the century, it was hypothesized that the majority, if not all, pathological events in AD are linked to free radical damage. Notably, free radicals also possess signaling capabilities that contribute to the disease's progression. A substantial body of evidence suggests that radical signaling is implicated in the relationship between amyloid-β and tau hyperphosphorylation. Antioxidant therapy represents a potential strategy to delay the progression from cognitive impairment to overt dementia. Enhancing endogenous antioxidant defenses, for instance, through polyphenol supplementation, offers a promising approach to partially prevent dementia onset, particularly in at-risk populations. Understanding the redox-related pathophysiology of AD opens new avenues for prevention and treatment, providing a source of hope in the fight against Alzheimer's Disease.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":7.1000,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Free radicals in Alzheimer's disease: from pathophysiology to clinical trial results.\",\"authors\":\"José Viña, Consuelo Borrás, Cristina Mas-Bargues\",\"doi\":\"10.1016/j.freeradbiomed.2024.09.051\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>In this review, we examine the role of oxidative stress in the pathophysiology of Alzheimer's Disease (AD). Amyloid-beta (Aβ) induces damage not only extracellularly but also within the intracellular environment. Mitochondria, a principal source of free radicals, are closely associated with Aβ, as it binds to heme, thereby disrupting the normal electron flow in the respiratory chain. At the turn of the century, it was hypothesized that the majority, if not all, pathological events in AD are linked to free radical damage. Notably, free radicals also possess signaling capabilities that contribute to the disease's progression. A substantial body of evidence suggests that radical signaling is implicated in the relationship between amyloid-β and tau hyperphosphorylation. Antioxidant therapy represents a potential strategy to delay the progression from cognitive impairment to overt dementia. Enhancing endogenous antioxidant defenses, for instance, through polyphenol supplementation, offers a promising approach to partially prevent dementia onset, particularly in at-risk populations. Understanding the redox-related pathophysiology of AD opens new avenues for prevention and treatment, providing a source of hope in the fight against Alzheimer's Disease.</p>\",\"PeriodicalId\":12407,\"journal\":{\"name\":\"Free Radical Biology and Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":7.1000,\"publicationDate\":\"2024-10-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Free Radical Biology and Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.freeradbiomed.2024.09.051\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Free Radical Biology and Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.freeradbiomed.2024.09.051","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
在这篇综述中,我们将探讨氧化应激在阿尔茨海默病(AD)病理生理学中的作用。淀粉样蛋白-β(Aβ)不仅在细胞外而且在细胞内环境中都会诱发损伤。线粒体是自由基的主要来源,它与 Aβ 密切相关,因为 Aβ 会与血红素结合,从而破坏呼吸链中的正常电子流。本世纪初,有人假设,注意力缺失症的大多数病理现象(如果不是全部的话)都与自由基损伤有关。值得注意的是,自由基还具有信号传导能力,有助于疾病的发展。大量证据表明,自由基信号传导与淀粉样蛋白-β和 tau 过度磷酸化之间的关系有关。抗氧化疗法是延缓认知障碍向明显痴呆发展的潜在策略。例如,通过补充多酚来增强内源性抗氧化防御能力,为部分预防痴呆症的发生(尤其是在高危人群中)提供了一种很有前景的方法。了解与氧化还原相关的老年痴呆症病理生理学为预防和治疗开辟了新途径,为防治老年痴呆症带来了希望。
Free radicals in Alzheimer's disease: from pathophysiology to clinical trial results.
In this review, we examine the role of oxidative stress in the pathophysiology of Alzheimer's Disease (AD). Amyloid-beta (Aβ) induces damage not only extracellularly but also within the intracellular environment. Mitochondria, a principal source of free radicals, are closely associated with Aβ, as it binds to heme, thereby disrupting the normal electron flow in the respiratory chain. At the turn of the century, it was hypothesized that the majority, if not all, pathological events in AD are linked to free radical damage. Notably, free radicals also possess signaling capabilities that contribute to the disease's progression. A substantial body of evidence suggests that radical signaling is implicated in the relationship between amyloid-β and tau hyperphosphorylation. Antioxidant therapy represents a potential strategy to delay the progression from cognitive impairment to overt dementia. Enhancing endogenous antioxidant defenses, for instance, through polyphenol supplementation, offers a promising approach to partially prevent dementia onset, particularly in at-risk populations. Understanding the redox-related pathophysiology of AD opens new avenues for prevention and treatment, providing a source of hope in the fight against Alzheimer's Disease.
期刊介绍:
Free Radical Biology and Medicine is a leading journal in the field of redox biology, which is the study of the role of reactive oxygen species (ROS) and other oxidizing agents in biological systems. The journal serves as a premier forum for publishing innovative and groundbreaking research that explores the redox biology of health and disease, covering a wide range of topics and disciplines. Free Radical Biology and Medicine also commissions Special Issues that highlight recent advances in both basic and clinical research, with a particular emphasis on the mechanisms underlying altered metabolism and redox signaling. These Special Issues aim to provide a focused platform for the latest research in the field, fostering collaboration and knowledge exchange among researchers and clinicians.