{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T04:41:04Z","timestamp":1786250464677,"version":"build-2736575974"},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T00:00:00Z","timestamp":1675641600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010275","name":"Deutsche Gesellschaft f\u00fcr Muskelkranke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010275","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013465","name":"French Muscular Dystrophy Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013465","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009591","name":"Ministerium f\u00fcr Innovation, Wissenschaft und Forschung des Landes Nordrhein-Westfalen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009591","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Chloroquine (CQ) is an antimalarial drug with a growing number of applications as recently demonstrated in attempts to treat Covid\u201019. For decades, it has been well known that skeletal and cardiac muscle cells might display vulnerability against CQ exposure resulting in the clinical manifestation of a CQ\u2010induced myopathy. In line with the known effect of CQ on inhibition of the lysosomal function and thus cellular protein clearance, the build\u2010up of autophagic vacuoles along with protein aggregates is a histological hallmark of the disease. Given that protein targets of the perturbed proteostasis are still not fully discovered, we applied different proteomic and immunological\u2010based studies to improve the current understanding of the biochemical nature of CQ\u2010myopathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To gain a comprehensive understanding of the molecular pathogenesis of this acquired myopathy and to define proteins targets as well as pathophysiological processes beyond impaired proteolysis, utilising CQ\u2010treated C2C12 cells and muscle biopsies derived from CQ\u2010myopathy patients, we performed different proteomic approaches and Coherent Anti\u2010Stokes Raman Scattering (CARS) microscopy, in addition to immunohistochemical studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our combined studies confirmed an impact of CQ\u2010exposure on proper protein processing\/folding and clearance, highlighted changes in the interactome of p62, a known aggregation marker and hereby identified the Rett syndrome protein MeCP2 as being affected. Moreover, our approach revealed\u2014among others\u2014a vulnerability of the extracellular matrix, cytoskeleton and lipid homeostasis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We demonstrated that CQ exposure (secondarily) impacts biological processes beyond lysosomal function and linked a variety of proteins with known roles in the manifestation of other neuromuscular diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12877","type":"journal-article","created":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T10:25:20Z","timestamp":1673519120000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Molecular mechanisms in chloroquine\u2010exposed muscle cells elucidated by combined proteomic and microscopic studies"],"prefix":"10.1111","volume":"49","author":[{"given":"Vietxuan","family":"Phan","sequence":"first","affiliation":[{"name":"Leibniz Institut f\u00fcr Analytische Wissenschaften \u2010ISAS\u2010 e.V.  Dortmund Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denisa","family":"Hathazi","sequence":"additional","affiliation":[{"name":"Leibniz Institut f\u00fcr Analytische Wissenschaften \u2010ISAS\u2010 e.V.  Dortmund Germany"},{"name":"Department of Clinical Neurosciences, School of Clinical Medicine University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5494-8150","authenticated-orcid":false,"given":"Corinna","family":"Preu\u00dfe","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin, Department of Neuropathology  Berlin Germany"},{"name":"Department of Neurology with Institute for Translational Neurology University Hospital M\u00fcnster  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artur","family":"Czech","sequence":"additional","affiliation":[{"name":"Leibniz Institut f\u00fcr Analytische Wissenschaften \u2010ISAS\u2010 e.V.  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Dortmund Germany"},{"name":"Manitoba Centre for Proteomics and Systems Biology Department of Internal Medicine Department of Biochemistry and Medical Genetics CancerCare Manitoba Research Institute University of Manitoba  Winnipeg MB Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2833-0928","authenticated-orcid":false,"given":"Andreas","family":"Roos","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics, Developmental Neurology and Social Pediatrics, Centre for Neuromuscular Disorders in Children, University Hospital Essen University of Duisburg\u2010Essen  Essen Germany"},{"name":"Children's Hospital of Eastern Ontario Research Institute University of Ottawa  Ottawa 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