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Emerging evidence indicates reduced activity of protein phosphatase 2A (PP2A), a heterotrimeric enzyme regulating dephosphorylation of serine/threonine residues, across lung cancer, smoke-induced COPD, alpha-1 antitrypsin deficiency, asthma, and idiopathic pulmonary fibrosis. Loss of PP2A signaling links to senescence, proliferation, inflammation, corticosteroid resistance, enhanced protease responses, and mRNA stability. Restoring PP2A activity may enable new treatments, supported by ongoing development of PP2A-directed therapeutics and specific activators targeting PP2A holoenzymes.",{"@graph":69,"@context":123},[70,84,106],{"@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/protein-phosphatase-2a-as-a-therapeutic-target-in-pulmonary-diseases/384063/",{"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/protein-phosphatase-2a-as-a-therapeutic-target-in-pulmonary-diseases/384063.png","ImageObject",300,407,{"name":92,"@type":93},"Adam","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-28","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why is protein phosphatase 2A (PP2A) considered a therapeutic target in pulmonary diseases?","Question",{"text":113,"@type":114},"Reduced PP2A activity is reported across multiple pulmonary conditions, including lung cancer and COPD. The review links PP2A loss to mechanisms driving disease progression, suggesting that restoring PP2A responses could offer therapeutic benefit.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Which pulmonary diseases are associated with reduced PP2A activity?",{"text":118,"@type":114},"The abstract highlights lung cancer, smoke-induced chronic obstructive pulmonary disease, alpha-1 antitrypsin deficiency, asthma, and idiopathic pulmonary fibrosis.",{"name":120,"@type":111,"acceptedAnswer":121},"What therapeutic strategy does the review propose to address PP2A loss?",{"text":122,"@type":114},"It proposes chemical restoration of PP2A, including developing specific activators that selectively target PP2A holoenzymes to restore normal PP2A responses in the lung.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},384063,1790619604,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":26},1374404737137,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","medicina  \nReview  \nProtein Phosphatase 2A as a Therapeutic Target in Pulmonary Diseases  \nHoward Yu 1, Sahil Zaveri 1, Zeeshan Sattar 1, Michael Schaible 1, Brais Perez Gandara 1, Anwar Uddin 1, Lucas R. McGarvey 1, Michael Ohlmeyer 2 and Patrick Geraghty 1, *  \nCitation: Yu, H.; Zaveri, S.; Sattar, Z.; Schaible, M.; Perez Gandara, B.; Uddin, A.; McGarvey, L.R.; Ohlmeyer, M.; Geraghty, P. Protein Phosphatase 2A as a Therapeutic Target in Pulmonary Diseases. Medicina 2023, 59, 1552. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)medicina59091552  \nAcademic Editor: Hisao Imai  \n1 Department of Medicine, State University of New York Downstate Health Sciences University, 450 Clarkson  \nAvenue, Brooklyn, NY 11203, USA; [howard.yu@downstate.edu](howard.yu@downstate.edu) (H.Y.); [sahil.zaveri@downstate.edu](sahil.zaveri@downstate.edu) (S.Z.);  \n[zsattar@kumc.edu](zsattar@kumc.edu) (Z.S.); [michael.schaible@downstate.edu](michael.schaible@downstate.edu) (M.S.);  \n[brais.perezgandara@downstate.edu](brais.perezgandara@downstate.edu) (B.P.G.); [anwar.uddin@downstate.edu](anwar.uddin@downstate.edu) (A.U.);  \n[panda.ant635@gmail.com](panda.ant635@gmail.com) (L.R.M.)  \n2 Atux Iskay LLC, Plainsboro, NJ 08536, USA; [michael.ohlmeyer@gmail.com](michael.ohlmeyer@gmail.com)  \n* [Correspondence: patrick.geraghty@downstate.edu](Correspondence: patrick.geraghty@downstate.edu); Tel.: +1-718-270-3141  \nAbstract: New disease targets and medicinal chemistry approaches are urgently needed to develop novel therapeutic strategies for treating pulmonary diseases. Emerging evidence suggests that reduced activity of protein phosphatase 2A (PP2A), a complex heterotrimeric enzyme that regulates dephosphorylation of serine and threonine residues from many proteins, is observed in multiple pulmonary diseases, including lung cancer, smoke-induced chronic obstructive pulmonary disease, alpha-1 antitrypsin deficiency, asthma, and idiopathic pulmonary fibrosis. Loss of PP2A responses is linked to many mechanisms associated with disease progressions, such as senescence, proliferation, inflammation, corticosteroid resistance, enhanced protease responses, and mRNA stability. Therefore, chemical restoration of PP2A may represent a novel treatment for these diseases. This review outlines the potential impact of reduced PP2A activity in pulmonary diseases, endogenous and exogenous inhibitors of PP2A, details the possible PP2A-dependent mechanisms observed in these conditions, and outlines potential therapeutic strategies for treatment. Substantial medicinal chemistry efforts are underway to develop therapeutics targeting PP2A activity. The development of specific activators of PP2A that selectively target PP2A holoenzymes could improve our understanding of the function of PP2A in pulmonary diseases. This may lead to the development of therapeutics for restoring normal PP2A responses within the lung.  \nKeywords: PP2A; lung diseases; inflammation; future therapy  \n1. Introduction  \nReceived: 25 July 2023  \nRevised: 22 August 2023  \nAccepted: 24 August 2023  \nPublished: 26 August 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \nChronic respiratory disorders affect the lungs, airways, and other structural components, leading to widespread illness and mortality. Lung cancer, asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF) are some of these respiratory conditions, and are among the top causes of morbidity and mortality worldwide. From 1990 to 2017, there was an increase in the prevalence of chronic lung disease worldwide. In 2017, 544.9 million individuals worldwide were impacted by chronic r","cbCaisvtlIS2jQg6","https://ap.wps.com/l/cbCaisvtlIS2jQg6","pdf",1087603,24,"English","# Introduction\n# Review\n## Abstract\n## Keywords","[{\"question\":\"Why is protein phosphatase 2A (PP2A) considered a therapeutic target in pulmonary diseases?\",\"answer\":\"Reduced PP2A activity is reported across multiple pulmonary conditions, including lung cancer and COPD. The review links PP2A loss to mechanisms driving disease progression, suggesting that restoring PP2A responses could offer therapeutic benefit.\"},{\"question\":\"Which pulmonary diseases are associated with reduced PP2A activity?\",\"answer\":\"The abstract highlights lung cancer, smoke-induced chronic obstructive pulmonary disease, alpha-1 antitrypsin deficiency, asthma, and idiopathic pulmonary fibrosis.\"},{\"question\":\"What therapeutic strategy does the review propose to address PP2A loss?\",\"answer\":\"It proposes chemical restoration of PP2A, including developing specific activators that selectively target PP2A holoenzymes to restore normal PP2A responses in the lung.\"}]","Protein Phosphatase 2A as a Therapeutic Target in Pulmonary Diseases | PDF",1790261045]