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The review details how ADAR1 isoforms p150 and p110 regulate signaling pathways involving MDA5, MAVS, and PKR, and how loss-of-function variants contribute to Aicardi-Goutières syndrome. It further summarizes ADAR1-mediated regulation across immune, nervous, respiratory, blood, and digestive systems and its impact on disease progression, cell differentiation, and treatment intervention prospects.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/the-role-of-adar1-in-human-pathophysiology-comprehensive-review/410876/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/the-role-of-adar1-in-human-pathophysiology-comprehensive-review/410876.png","ImageObject",300,407,{"name":92,"@type":93},"Angel","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is ADAR1 and what biological reaction does it catalyze?","Question",{"text":112,"@type":113},"ADAR1 is an enzyme that acts on double-stranded RNA and catalyzes adenosine-inosine (A-to-I) deamination/editing of dsRNA.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How do the two main ADAR1 isoforms (p110 and p150) influence innate immunity?",{"text":117,"@type":113},"p150 primarily prevents inappropriate recognition of cytosolic dsRNA by suppressing MDA5 activation through editing-dependent and editing-independent mechanisms, thereby limiting type I interferon responses. p110 is more prominent in the nucleus and supports stress survival by editing and stabilizing specific mRNA transcripts.",{"name":119,"@type":110,"acceptedAnswer":120},"What human disease is linked to loss-of-function mutations in ADAR1?",{"text":121,"@type":113},"Loss-of-function mutations in ADAR1 in humans cause Aicardi-Goutières syndrome (AGS), a severe autoinflammatory disorder characterized by chronic interferon signaling.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},410876,1790767665,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":26,"preview_page_count":4},687207412472,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","TYPE Review  \nPUBLISHED 18 December 2025 DOI 10.3389/fcell.2025.1672970  \nOPEN ACCESS  \nEDITED BY  \nEfthimios M. C. Skoulakis,  \nAlexander Fleming Biomedical Sciences Research Center, Greece  \nREVIEWED BY  \nZhijie Song,  \nShenyang Medical College, China Arlan Silva Freitas,  \nFederal Institute of Education, Science and Technology of Maranhão, Brazil  \n*CORRESPONDENCE  \nYan Dai,  \n [daiyan@swmu.edu.cn](daiyan@swmu.edu.cn)  \nRECEIVED 14 August 2025  \nREVISED 24 November 2025  \nACCEPTED 28 November 2025  \nPUBLISHED 18 December 2025  \nCITATION  \nLi J, Xiao Y, Li X and Dai Y (2025) The role of ADAR1 in human pathophysiology.  \nFront. Cell Dev. Biol. 13:1672970 .  \ndoi: 10.3389/fcell.2025.1672970  \nCOPYRIGHT  \n© 2025 Li, Xiao, Li and Dai. This is an  \nopen-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nThe role of ADAR1 in human pathophysiology  \nJiahao Li 1, Yushan Xiao 1, Xiaofeng Li 1 and Yan Dai 2*  \n1School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China, 2 Department of pharmacy, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China  \nAdenosine deaminase 1 (ADAR1) is an enzyme acting on double-stranded RNA, primarily responsible for catalyzing the adenosine-inosine deamination reaction of dsRNA.An increasing number of studies have demonstrated that ADAR1 plays a pivotal role in various diseases, including cardiovascular, neurological, and immune disorders, among others. Some of these diseases remain incurable. In addition, ADAR1 is also involved in the development and differentiation of various crucial cells, such as hematopoietic stem cells and nerve cells. This article comprehensively summarizes the regulatory effects of ADAR1 on crucial cells and organs across the immune, nervous, respiratory, blood, and digestive systems, along with its influence on disease progression. The aim is to offer assistance in intervening in cells and treating diseases.  \nKEYWORDS  \nADAR1, human diseases, physiological process, immunity, cancer  \n1 Introduction  \nADAR1 acts on RNA, catalyzing the A-I deamination reaction on double-stranded RNA molecules, thereby regulating cellular responses to both endogenous and exogenous RNAs (Sun et al., 2021) . ADAR1 is involved in the regulation of the growth and development of cells and organs in the nervous system, respiratory system, digestive system, circulatory system, immune system, endocrine system and the maintenance of homeostasis. Its expression also affects the progression of diseases in various systems. As shown in Figure 1. In addition, we summarize the impact of ADAR1 on various viruses or human diseases. As shown in Table 1.  \nADAR1, through its two principal isoforms p110 and p150, serves as a critical gatekeeper in maintaining innate immune homeostasis by preventing inappropriate recognition of dsRNA (Sun et al., 2021). The interferon-inducible p150 isoform, localized predominantly in the cytoplasm, is the primary defense against cytosolic dsRNA sensors. It suppresses the activation of melanoma differentiation-associated gene 5 (MDA5) through both editing-dependent and editing-independent mechanisms. By catalyzing A-to-I RNA editing on endogenous dsRNAs, ADAR1 p150 destabilizes the duplex structure, thereby masking ‘self’ RNA from MDA5 recognition and preventing the initiation of a deleterious type I interferon response via the MAVS signaling pathway (de Reuver and Maelfait, 2024) . Genetic evidence underscores this vital role, as lossof-function mutations in ADAR1 in humans lead to Aicardi-Goutières syndrome (AGS), a severe autoinflammatory disorder characterized by ch","cbCail9iufCSjgBk","https://ap.wps.com/l/cbCail9iufCSjgBk","pdf",6298974,24,"English","# Introduction\n## ADAR1 isoforms and dsRNA sensing\n## Innate immune homeostasis via MDA5 and PKR\n## Immune, nervous, and other system regulation\n# Cell and disease progression overview\n## Hematopoietic stem cells and nerve cells\n## Cancer and stress-related survival","[{\"question\":\"What is ADAR1 and what biological reaction does it catalyze?\",\"answer\":\"ADAR1 is an enzyme that acts on double-stranded RNA and catalyzes adenosine-inosine (A-to-I) deamination/editing of dsRNA.\"},{\"question\":\"How do the two main ADAR1 isoforms (p110 and p150) influence innate immunity?\",\"answer\":\"p150 primarily prevents inappropriate recognition of cytosolic dsRNA by suppressing MDA5 activation through editing-dependent and editing-independent mechanisms, thereby limiting type I interferon responses. p110 is more prominent in the nucleus and supports stress survival by editing and stabilizing specific mRNA transcripts.\"},{\"question\":\"What human disease is linked to loss-of-function mutations in ADAR1?\",\"answer\":\"Loss-of-function mutations in ADAR1 in humans cause Aicardi-Goutières syndrome (AGS), a severe autoinflammatory disorder characterized by chronic interferon signaling.\"}]","The role of ADAR1 in human pathophysiology - Comprehensive review | PDF",1790586689]