{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:38:53Z","timestamp":1767832733123,"version":"3.49.0"},"reference-count":71,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T00:00:00Z","timestamp":1690156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Atopic dermatitis (AD) is the most common chronic relapsing neuroinflammatory skin disease that is characterized by a complex and multifactorial pathophysiology. It reflects a profound interplay between genetic and environmental factors, and a recently disclosed neuroimmune dysregulation that drives skin barrier disruption, pruritus, and microbial imbalance. In terms of the key external environmental players that impact AD, air quality and itch severity linkage have been thoroughly researched. The impact of ambient air pollutants including particulate matter (PM) and AD pruritic exacerbation has been recorded despite reductions in air pollution levels in in developed countries. The developing countries have, on the contrary, experienced significant urbanization and industrialization with limited environmental protection standards in the past decades. This unprecedented construction, petrochemical industry utilization, and increment in population counts has been paired with consistent exposure to outdoor PM. This may present a key cause of AD pruritic exacerbation supported by the fact that AD prevalence has intensified globally in the past 50 years, indicating that environmental exposure may act as a trigger that could flare up itch in vulnerable persons. At the molecular level, the impact of PM on severe pruritus in AD could be interpreted by the toxic effects on the complex neuroimmune pathways that govern this disease. AD has been recently viewed as a manifestation of the disruption of both the immune and neurological systems. In light of these facts, this current review aims to introduce the basic concepts of itch sensory circuits in the neuroimmune system. In addition, it describes the impact of PM on the potential neuroimmune pathways in AD pathogenesis with a special focus on the Fc Epsilon RI pathway. Finally, the review proposes potential treatment lines that could be targeted to alleviate pruritus based on immune mediators involved in the Fc Epsilon signaling map.<\/jats:p>","DOI":"10.3390\/ijms241411851","type":"journal-article","created":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T01:21:27Z","timestamp":1690248087000},"page":"11851","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Fc Epsilon RI\u2013Neuroimmune Interplay in Pruritus Triggered by Particulate Matter in Atopic Dermatitis Patients"],"prefix":"10.3390","volume":"24","author":[{"given":"Dina","family":"Isaifan","sequence":"first","affiliation":[{"name":"Department of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8493-1168","authenticated-orcid":false,"given":"Sergio","family":"Crovella","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Research Center (LARC), Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1129-4513","authenticated-orcid":false,"given":"Lama","family":"Soubra","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9354-0214","authenticated-orcid":false,"given":"Maryam","family":"Al-Nesf","sequence":"additional","affiliation":[{"name":"Allergy and Immunology Division, Hamad Medical Corporation, Doha P.O. Box 3050, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Steinhoff","sequence":"additional","affiliation":[{"name":"Department of Dermatology & Venereology, Weill Cornell Medicine, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"959","DOI":"10.2147\/CCID.S289716","article-title":"Current clinical options for the management of itch in atopic dermatitis","volume":"14","author":"Lipman","year":"2021","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1111\/j.1365-2133.2008.08941.x","article-title":"Itch characteristics in atopic dermatitis: Results of a web-based questionnaire","volume":"160","author":"Dawn","year":"2009","journal-title":"Br. J. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1159\/000370220","article-title":"Atopic dermatitis: Global epidemiology and risk factors","volume":"66","author":"Nutten","year":"2015","journal-title":"Ann. Nutr. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2727","DOI":"10.3389\/fimmu.2018.02727","article-title":"Leveraging multilayered \u201comics\u201d data for atopic dermatitis: A road map to precision medicine","volume":"9","author":"Ghosh","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.jaci.2016.02.045","article-title":"Resolving the Etiology of Atopic Disorders by Genetic Analysis of Racial Ancestry Jayanta","volume":"138","author":"Gupta","year":"2016","journal-title":"J. Clin. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1016\/j.jaci.2022.03.010","article-title":"Neuroimmune communication regulating pruritus in atopic dermatitis","volume":"149","author":"Steinhoff","year":"2022","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1080\/1744666X.2016.1212660","article-title":"Environmental risk factors and role in management of atopic dermatitis","volume":"13","author":"Kantor","year":"2017","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"341","DOI":"10.2340\/00015555-3512","article-title":"Disease mechanisms in atopic dermatitis: A review of aetiological factors","volume":"100","author":"Thyssen","year":"2020","journal-title":"Acta Derm. Venereol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Sroka-Tomaszewska, J., and Trzeciak, M. (2021). Molecular mechanisms of atopic dermatitis pathogenesis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22084130"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2829","DOI":"10.4049\/jimmunol.1801473","article-title":"The Neuroimmune Axis in Skin Sensation, Inflammation, and Immunity","volume":"202","author":"Trier","year":"2019","journal-title":"J. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1172\/JCI124609","article-title":"Neuro-immune crosstalk and allergic inflammation","volume":"129","author":"Kabata","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Rizzi, V., Gubitosa, J., Fini, P., and Cosma, P. (2021). Neurocosmetics in skincare-the fascinating world of skin-brain connection: A review to explore ingredients, commercial products for skin aging, and cosmetic regulation. Cosmetics, 8.","DOI":"10.3390\/cosmetics8030066"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"906755","DOI":"10.3389\/fcell.2022.906755","article-title":"Neuroimmune Interaction: A Widespread Mutual Regulation and the Weapons for Barrier Organs","volume":"10","author":"Zhu","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1080\/14728222.2017.1328057","article-title":"Targeting dorsal root ganglia and primary sensory neurons for the treatment of chronic pain","volume":"21","author":"Berta","year":"2017","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.2147\/JAA.S282039","article-title":"Further Understanding of Neuro-Immune Interactions in Allergy: Implications in Pathophysiology and Role in Disease Progression","volume":"15","author":"Konstantinou","year":"2022","journal-title":"J. Asthma Allergy"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1038\/nature06029","article-title":"A gastrin-releasing peptide receptor mediates the itch sensation in the spinal cord","volume":"448","author":"Sun","year":"2007","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/s40257-015-0171-3","article-title":"Quality of Life in Patients with Atopic Dermatitis: Disease Burden, Measurement, and Treatment Benefit","volume":"17","author":"Blome","year":"2016","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1111\/dth.12032","article-title":"The effects of treatment on itch in atopic dermatitis","volume":"26","author":"Yarbrough","year":"2013","journal-title":"Dermatol. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.immuni.2020.04.008","article-title":"Itch: A Paradigm of Neuroimmune Crosstalk","volume":"52","author":"Wang","year":"2020","journal-title":"Immunity"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Thangavel, P., Park, D., and Lee, Y.C. (2022). Recent Insights into Particulate Matter (PM2.5)-Mediated Toxicity in Humans: An Overview. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19127511"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.jaci.2017.02.001","article-title":"Synergistic antipruritic effects of gamma aminobutyric acid A and B agonists in a mouse model of atopic dermatitis","volume":"140","author":"Cevikbas","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1097\/JD9.0000000000000045","article-title":"Sensitization Mechanisms of Chronic Itch","volume":"2","author":"Jin","year":"2019","journal-title":"Int. J. Dermatol. Venereol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Fania, L., Moretta, G., Antonelli, F., Scala, E., Abeni, D., Albanesi, C., and Madonna, S. (2022). Multiple Roles for Cytokines in Atopic Dermatitis: From Pathogenic Mediators to Endotype-Specific Biomarkers to Therapeutic Targets. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052684"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e142067","DOI":"10.1172\/jci.insight.142067","article-title":"Cytokinocytes: The diverse contribution of keratinocytes to immune responses in skin","volume":"5","author":"Jiang","year":"2020","journal-title":"JCI Insight"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"100361","DOI":"10.1016\/j.bbih.2021.100361","article-title":"Roles of calcitonin gene-related peptide in the skin, and other physiological and pathophysiological functions","volume":"18","author":"Kim","year":"2021","journal-title":"Brain Behav. Immun. Health"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.envpol.2019.01.086","article-title":"The impacts of urbanization on fine particulate matter (PM2.5) concentrations: Empirical evidence from 135 countries worldwide","volume":"247","author":"Wang","year":"2019","journal-title":"Environ. Pollut."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1111\/pai.12543","article-title":"Association of pollution and climate with atopic eczema in US children","volume":"27","author":"Kathuria","year":"2016","journal-title":"Pediatr. Allergy Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"101545","DOI":"10.1016\/j.redox.2020.101545","article-title":"Oxidative stress pathways of air pollution mediated toxicity: Recent insights","volume":"34","author":"Gangwar","year":"2020","journal-title":"Redox Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"101530","DOI":"10.1016\/j.redox.2020.101530","article-title":"The aryl hydrocarbon receptor as a target of environmental stressors\u2014Implications for pollution mediated stress and inflammatory responses","volume":"34","author":"Vogel","year":"2020","journal-title":"Redox Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1007\/s13555-019-00332-3","article-title":"Epidemiology, Diagnosis, and Treatment of Atopic Dermatitis in the Developing Countries of Asia, Africa, Latin America, and the Middle East: A Review","volume":"9","author":"Carrera","year":"2019","journal-title":"Dermatol. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.1111\/bph.12414","article-title":"Transient receptor potential [TRP] channels: A clinical perspective","volume":"171","author":"Kaneko","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"271","DOI":"10.3389\/fncel.2019.00271","article-title":"Human dorsal root ganglia","volume":"13","author":"Haberberger","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.autneu.2010.03.004","article-title":"Afferent nerve fibers and acupuncture","volume":"157","author":"Kagitani","year":"2010","journal-title":"Auton. Neurosci. Basic Clin."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.molimm.2014.01.018","article-title":"Mast cell progenitors: Origin, development and migration to tissues","volume":"63","author":"Dahlin","year":"2015","journal-title":"Mol. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.cellsig.2019.01.010","article-title":"Fine particulate matter [PM 2.5] enhances Fc\u03b5RI-mediated signaling and mast cell function","volume":"57","author":"Jin","year":"2019","journal-title":"Cell. Signal."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"18408","DOI":"10.1074\/jbc.M601535200","article-title":"Negative regulation of Fc\u03b5RI-mediated signaling and mast cell function by the adaptor protein LAX","volume":"281","author":"Zhu","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1084\/jem.20061598","article-title":"An essential role for RasGRP1 in mast cell function and IgE-mediated allergic response","volume":"204","author":"Liu","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"32891","DOI":"10.1074\/jbc.R110.205104","article-title":"Immunoglobulin E receptor signaling and asthma","volume":"286","author":"Wu","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s12974-022-02417-x","article-title":"Neuronal Fc\u03b5RI\u03b1 directly mediates ocular itch via IgE-immune complex in a mouse model of allergic conjunctivitis","volume":"19","author":"Cui","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1002\/art.41386","article-title":"Fc\u03b3 Receptor I\u2013Coupled Signaling in Peripheral Nociceptors Mediates Joint Pain in a Rat Model of Rheumatoid Arthritis","volume":"72","author":"Liu","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Yashiro, T., Ogata, H., Zaidi, S.F., Lee, J., Hayashi, S., Yamamoto, T., and Kadowaki, M. (2021). Pathophysiological roles of neuro-immune interactions between enteric neurons and mucosal mast cells in the gut of food allergy mice. Cells, 10.","DOI":"10.3390\/cells10071586"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/cei\/uxac097","article-title":"Signals from the TAFA4-PTEN-PU.1 axis alleviate nasal allergy by modulating the expression of Fc\u03b5RI in mast cells","volume":"211","author":"Zhou","year":"2022","journal-title":"Clin. Exp. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"262","DOI":"10.3389\/fncel.2019.00262","article-title":"Secretion of mast cell inflammatory mediators is enhanced by CADM1-dependent adhesion to sensory neurons","volume":"13","author":"Magadmi","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Kaplan, G., Avdan, Z.Y., and Avdan, U. (2019). Spaceborne Nitrogen Dioxide Observations from the Sentinel-5P TROPOMI over Turkey. Proceedings, 18.","DOI":"10.3390\/ECRS-3-06181"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"84","DOI":"10.2500\/aap.2019.40.4202","article-title":"Pathophysiology of atopic dermatitis: Clinical implications","volume":"40","author":"Kim","year":"2019","journal-title":"Allergy Asthma Proc."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1038\/s41375-020-0805-1","article-title":"Dasatinib vs. imatinib in patients with chronic myeloid leukemia in chronic phase [CML-CP] who have not achieved an optimal response to 3 months of imatinib therapy: The DASCERN randomized study","volume":"34","author":"Cortes","year":"2020","journal-title":"Leukemia"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1186\/s13045-017-0512-1","article-title":"Syk inhibitors in clinical development for hematological malignancies","volume":"10","author":"Liu","year":"2017","journal-title":"J. Hematol. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s40267-018-0551-x","article-title":"Fostamatinib in chronic immune thrombocytopenia: A profile of its use in the USA","volume":"34","author":"McKeage","year":"2018","journal-title":"Drugs Ther. Perspect."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"H\u00e4fliger, P., and Charles, R.P. (2019). The l-type amino acid transporter LAT1\u2014An emerging target in cancer. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20102428"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/1010428317694545","article-title":"Inhibition of l-type amino acid transporter 1 activity as a new therapeutic target for cholangiocarcinoma treatment","volume":"39","author":"Yothaisong","year":"2017","journal-title":"Tumor Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"81","DOI":"10.2147\/BLCTT.S326627","article-title":"Use of BTK Inhibitors in Chronic Lymphocytic Leukemia\/Small Lymphocytic Lymphoma [CLL\/SLL]: A Practical Guidance","volume":"12","author":"Ma","year":"2022","journal-title":"Blood Lymphat. Cancer Targets Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.3892\/ol.2017.5564","article-title":"The associated pyrazolopyrimidines PP1 and PP2 inhibit protein tyrosine kinase 6 activity and suppress breast cancer cell proliferation","volume":"13","author":"Shim","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s13045-021-01127-w","article-title":"Emerging strategies to target RAS signaling in human cancer therapy","volume":"14","author":"Chen","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"115","DOI":"10.2147\/LCTT.S334623","article-title":"Spotlight on sotorasib [Amg 510] for krasg12c positive non-small cell lung cancer","volume":"12","author":"Zhang","year":"2021","journal-title":"Lung Cancer Targets Ther."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"39185","DOI":"10.18632\/oncotarget.16642","article-title":"PDK1 inhibitor GSK2334470 exerts antitumor activity in multiple myeloma and forms a novel multitargeted combination with dual mTORC1\/C2 inhibitor PP242","volume":"8","author":"Yang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"34586","DOI":"10.18632\/oncotarget.16656","article-title":"Discovery and characterization of small molecule Rac1 inhibitors","volume":"8","author":"Arnst","year":"2017","journal-title":"Oncotarget"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"35666","DOI":"10.1074\/jbc.M703571200","article-title":"Specificity and mechanism of action of EHT 1864, a novel small molecule inhibitor of Rac family small GTPases","volume":"282","author":"Shutes","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"199","DOI":"10.2217\/mmt.15.21","article-title":"Dabrafenib and its use in the treatment of metastatic melanoma","volume":"2","author":"Bowyer","year":"2015","journal-title":"Melanoma Manag."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1186\/s13045-020-01025-7","article-title":"MEK inhibitors for the treatment of non-small cell lung cancer","volume":"14","author":"Han","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/1753466618767611","article-title":"Dabrafenib in combination with trametinib in the treatment of patients with BRAF V600-positive advanced or metastatic non-small cell lung cancer: Clinical evidence and experience","volume":"12","author":"Khunger","year":"2018","journal-title":"Ther. Adv. Respir. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1111\/cei.12225","article-title":"The protein kinase C inhibitor sotrastaurin allows regulatory T cell function","volume":"175","author":"Kho","year":"2014","journal-title":"Clin. Exp. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1080\/14756366.2020.1720013","article-title":"Selective inhibitors for JNK signaling: A potential targeted therapy in cancer","volume":"35","author":"Wu","year":"2020","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1111\/sji.12333","article-title":"Targets for Ibrutinib Beyond B Cell Malignancies","volume":"82","author":"Hamasy","year":"2015","journal-title":"Scand. J. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1021\/acs.oprd.1c00113","article-title":"Solid Form Selection and Process Development of KO-947 Drug Substances","volume":"25","author":"Mei","year":"2021","journal-title":"Org. Process Res. Dev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/s41419-020-2229-2","article-title":"Targeting Src family kinase member Fyn by Saracatinib attenuated liver fibrosis in vitro and in vivo","volume":"11","author":"Du","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1001\/jamaneurol.2019.2050","article-title":"Effect of AZD0530 on Cerebral Metabolic Decline in Alzheimer Disease: A Randomized Clinical Trial","volume":"76","author":"Nygaard","year":"2019","journal-title":"JAMA Neurol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/s41573-021-00209-1","article-title":"PI3K inhibitors are finally coming of age","volume":"20","author":"Vanhaesebroeck","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_68","first-page":"768","article-title":"Alpelisib: A Novel Therapy for","volume":"11","author":"Wilhoit","year":"2020","journal-title":"J. Adv. Pract. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s12974-015-0311-y","article-title":"Oral administration of cytosolic PLA2 inhibitor arachidonyl trifluoromethyl ketone ameliorates cauda equina compression injury in rats","volume":"12","author":"Khan","year":"2015","journal-title":"J. Neuroinflamm."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"662232","DOI":"10.3389\/fphar.2021.662232","article-title":"AKT Inhibitors: New Weapons in the Fight Against Breast Cancer?","volume":"12","author":"Martorana","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1042\/BST20190777","article-title":"Inhibitors in AKTion: ATP-competitive vs allosteric","volume":"48","author":"Lazaro","year":"2020","journal-title":"Biochem. Soc. Trans."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/14\/11851\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:17:58Z","timestamp":1760127478000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/14\/11851"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,24]]},"references-count":71,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["ijms241411851"],"URL":"https:\/\/doi.org\/10.3390\/ijms241411851","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,24]]}}}