{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:36:45Z","timestamp":1792798605623,"version":"4.5.0"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"NHMRC","doi-asserted-by":"publisher","award":["APP1086786"],"award-info":[{"award-number":["APP1086786"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"NHMRC","doi-asserted-by":"publisher","award":["APP2009957"],"award-info":[{"award-number":["APP2009957"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000864","name":"Michael J Fox Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shake it Up Australia Foundation","award":["9916"],"award-info":[{"award-number":["9916"]}]},{"name":"Shake it Up Australia Foundation","award":["12626"],"award-info":[{"award-number":["12626"]}]},{"DOI":"10.13039\/501100001134","name":"Australia India Strategic Research Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001134","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Inflazome Ltd"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Parkinson\u2019s disease is one of the fastest-growing neurodegenerative disorders, with no effective treatments to modify its progression. Microglial-driven neuroinflammation, mediated by NOD-leucine rich repeat and pyrin containing protein 3 (NLRP3) inflammasome activation, plays a key role in disease onset and progression. The NLRP3 inflammasome is upregulated in microglia from Parkinson\u2019s disease patients and activated by oxidative stress and \u03b1-synuclein aggregates, triggering the release of pro-inflammatory mediators that contribute to neuroinflammation and neuronal death. MCC950, the first described specific NLRP3 inhibitor, has shown promise in Parkinson\u2019s disease models but is limited by suboptimal pharmacokinetics and safety, hindering its clinical development.<\/jats:p>\n                  <jats:p>Here, we developed a novel NLRP3 inflammasome inhibitor, MCC7840 (also known as Inzomelid or Emlenoflast), and utilized clinically relevant PET-MRI imaging biomarkers to assess its therapeutic efficacy in preclinical models of Parkinson\u2019s disease.<\/jats:p>\n                  <jats:p>MCC7840 inhibited NLRP3 in human and mouse microglia with nanomolar potency, while demonstrating improved systemic exposure, half-life, brain permeability and bioavailability compared with MCC950. In a murine NLRP3 gain-of-function model of Muckle\u2013Wells syndrome, MCC7840 effectively inhibited mortality and demonstrated superior potency compared with MCC950. Chronic oral administration of MCC7840 protected against neuroinflammation, motor deficits and dopamine loss in both 6-hydroxydopamine and preformed \u03b1-synuclein fibril mouse models of Parkinson\u2019s disease. Radiotracer imaging of multiple PET markers in the same mouse revealed that MCC7840 attenuated neuroinflammation (translocator protein ligand; 18F-DPA-714), preserved dopamine uptake (fluorodopa; 18F-FDOPA), mitigated dopamine transporter (DAT) loss (DAT ligand; 18F-FBCTT) and reduced blood\u2013brain barrier leakage (gadolinium contrast MRI). Notably, MCC7840 was effective in a slowly progressing 12-month \u03b1-synuclein model, even when administered after symptom onset, 4 months post-\u03b1-synuclein injection.<\/jats:p>\n                  <jats:p>These findings highlight the utility of PET\/MRI as a non-invasive tool to evaluate drug efficacy and support MCC7840, and other brain-penetrant NLRP3 inhibitors, as promising disease-modifying therapies for Parkinson\u2019s disease, warranting future clinical investigation.<\/jats:p>","DOI":"10.1093\/brain\/awaf372","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T12:27:05Z","timestamp":1760531225000},"page":"1289-1301","source":"Crossref","is-referenced-by-count":8,"title":["PET-MRI biomarkers reveal efficacy of a novel NLRP3 inhibitor in Parkinson\u2019s disease models"],"prefix":"10.1093","volume":"149","author":[{"given":"Eduardo A","family":"Albornoz","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland , Brisbane 4072 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"Mardon","sequence":"additional","affiliation":[{"name":"Centre for Advanced Imaging, The University of Queensland , Brisbane 4072 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv","family":"Bhalla","sequence":"additional","affiliation":[{"name":"Centre for Advanced Imaging, The University of Queensland , Brisbane 4072 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinod","family":"Kumar","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland , Brisbane 4072 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damion H R","family":"Stimson","sequence":"additional","affiliation":[{"name":"Centre for Advanced Imaging, The University of Queensland , Brisbane 4072 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Cowin","sequence":"additional","affiliation":[{"name":"Centre for Advanced Imaging, The University of Queensland , Brisbane 4072 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cedric S","family":"Cui","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland , Brisbane 4072 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S","family":"Butler","sequence":"additional","affiliation":[{"name":"The Institute for Molecular Bioscience, The University of Queensland , Brisbane 4072 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruby","family":"Pelingon","sequence":"additional","affiliation":[{"name":"The Institute for Molecular Bioscience, The University of Queensland , Brisbane 4072 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Gordon","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland , Brisbane 4072 ,","place":["Australia"]},{"name":"Translational Research Institute (TRI), School of Biomedical Sciences, Faculty of Health, Queensland University of Technology , Brisbane 4102 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca C","family":"Coll","sequence":"additional","affiliation":[{"name":"The Institute for Molecular Bioscience, The University of Queensland , Brisbane 4072 ,","place":["Australia"]},{"name":"The Wellcome-Wolfson Institute for Experimental Medicine, Queen\u2019s University Belfast , Belfast BT9 7BL ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Schroder","sequence":"additional","affiliation":[{"name":"The Institute for Molecular Bioscience, The University of Queensland , Brisbane 4072 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reena","family":"Halai","sequence":"additional","affiliation":[{"name":"Inflazome Ltd , Welwyn Garden City AL7 1TW ,","place":["UK"]},{"name":"Sitala Bio Ltd. , Shelford, Cambridgeshire CB22 1LD ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angus M","family":"MacLeod","sequence":"additional","affiliation":[{"name":"Inflazome Ltd , Welwyn Garden City AL7 1TW ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Matthews","sequence":"additional","affiliation":[{"name":"Inflazome Ltd , Welwyn Garden City AL7 1TW ,","place":["UK"]},{"name":"Sitala Bio Ltd. , Shelford, Cambridgeshire CB22 1LD ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avril A B","family":"Robertson","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland , Brisbane 4072 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A","family":"Cooper","sequence":"additional","affiliation":[{"name":"Inflazome Ltd , Welwyn Garden City AL7 1TW ,","place":["UK"]},{"name":"Sitala Bio Ltd. , Shelford, Cambridgeshire CB22 1LD ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1382-911X","authenticated-orcid":false,"given":"Trent M","family":"Woodruff","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland , Brisbane 4072 ,","place":["Australia"]},{"name":"Queensland Brain Institute, The University of Queensland , Brisbane 4072 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"issue":"s1","key":"2026040804062993800_awaf372-B1","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.3233\/JPD-181474","article-title":"The emerging evidence of the Parkinson pandemic","volume":"8","author":"Dorsey","year":"2018","journal-title":"J Parkinsons Dis"},{"issue":"s1","key":"2026040804062993800_awaf372-B2","doi-asserted-by":"crossref","first-page":"S105","DOI":"10.3233\/JPD-223237","article-title":"Microglia in Parkinson\u2019s disease","volume":"12","author":"Stefanova","year":"2022","journal-title":"J 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