{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:30:51Z","timestamp":1791462651462,"version":"4.3.4"},"reference-count":39,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,11]],"date-time":"2023-06-11T00:00:00Z","timestamp":1686441600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Society for Muscle Diseases DGM","award":["GU1\/2"],"award-info":[{"award-number":["GU1\/2"]}]},{"name":"German Society for Muscle Diseases DGM","award":["F960R-2020"],"award-info":[{"award-number":["F960R-2020"]}]},{"name":"FoRUM program of the Ruhr-University Bochum","award":["GU1\/2"],"award-info":[{"award-number":["GU1\/2"]}]},{"name":"FoRUM program of the Ruhr-University Bochum","award":["F960R-2020"],"award-info":[{"award-number":["F960R-2020"]}]},{"name":"Heimer Foundation, Bielefeld","award":["GU1\/2"],"award-info":[{"award-number":["GU1\/2"]}]},{"name":"Heimer Foundation, Bielefeld","award":["F960R-2020"],"award-info":[{"award-number":["F960R-2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Pompe disease is a rare genetic metabolic disorder caused by mutations in acid-alpha glucoside (GAA) leading to pathological lysosomal glycogen accumulation associated with skeletal muscle weakness, respiratory difficulties and cardiomyopathy, dependent from the GAA residual enzyme activity. This study aimed to investigate early proteomic changes in a mouse model of Pompe disease and identify potential therapeutic pathways using proteomic analysis of skeletal muscles from pre-symptomatic Pompe mice. For this purpose, quadriceps samples of Gaa6neo\/6neo mutant (Pompe) and wildtype mice, at the age of six weeks, were studied with three biological replicates for each group. The data were validated with skeletal muscle morphology, immunofluorescence studies and western blot analysis. Proteomic profiling identified 538 significantly upregulated and 16 significantly downregulated proteins in quadriceps muscles derived from Pompe animals compared to wildtype mice. The majority of significantly upregulated proteins were involved in metabolism, translation, folding, degrading and vesicular transport, with some having crucial roles in the etiopathology of other neurological or neuromuscular diseases. This study highlights the importance of the early diagnosis and treatment of Pompe disease and suggests potential add-on therapeutic strategies targeting protein dysregulations.<\/jats:p>","DOI":"10.3390\/cells12121602","type":"journal-article","created":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T01:28:21Z","timestamp":1686533301000},"page":"1602","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dysregulation of Metabolism and Proteostasis in Skeletal Muscle of a Presymptomatic Pompe Mouse Model"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6168-4635","authenticated-orcid":false,"given":"Marlena","family":"Rohm","sequence":"first","affiliation":[{"name":"Department of Neurology, BG-University Hospital Bergmannsheil gGmbH, Ruhr-University Bochum, 44789 Bochum, Germany"},{"name":"Heimer Institute for Muscle Research, BG-University Hospital Bergmannsheil gGmbH, Ruhr-University Bochum, 44789 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7411-1301","authenticated-orcid":false,"given":"Leon","family":"Volke","sequence":"additional","affiliation":[{"name":"Department of Neurology, BG-University Hospital Bergmannsheil gGmbH, Ruhr-University Bochum, 44789 Bochum, Germany"},{"name":"Heimer Institute for Muscle Research, BG-University Hospital Bergmannsheil gGmbH, Ruhr-University Bochum, 44789 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0716-3780","authenticated-orcid":false,"given":"Lara","family":"Schlaffke","sequence":"additional","affiliation":[{"name":"Department of Neurology, BG-University Hospital Bergmannsheil gGmbH, Ruhr-University Bochum, 44789 Bochum, Germany"},{"name":"Heimer Institute for Muscle Research, BG-University Hospital Bergmannsheil gGmbH, Ruhr-University Bochum, 44789 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Rehmann","sequence":"additional","affiliation":[{"name":"Department of Neurology, BG-University Hospital Bergmannsheil gGmbH, Ruhr-University Bochum, 44789 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolina","family":"S\u00fcdkamp","sequence":"additional","affiliation":[{"name":"Department of Neurology, BG-University Hospital Bergmannsheil gGmbH, Ruhr-University Bochum, 44789 Bochum, Germany"},{"name":"Heimer Institute for Muscle Research, BG-University Hospital Bergmannsheil gGmbH, Ruhr-University Bochum, 44789 Bochum, Germany"}],"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 Neurology, BG-University Hospital Bergmannsheil gGmbH, Ruhr-University Bochum, 44789 Bochum, Germany"},{"name":"Heimer Institute for Muscle Research, BG-University Hospital Bergmannsheil gGmbH, Ruhr-University Bochum, 44789 Bochum, Germany"},{"name":"Department of Neuropediatrics, University Hospital Essen, Duisburg-Essen University, 45147 Essen, Germany"},{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON K1H 8L1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Sch\u00e4nzer","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, Justus Liebig University, 35390 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0272-9220","authenticated-orcid":false,"given":"Andreas","family":"Hentschel","sequence":"additional","affiliation":[{"name":"Leibniz-Institut f\u00fcr Analytische Wissenschaften, 44139 Dortmund, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1782-4642","authenticated-orcid":false,"given":"Matthias","family":"Vorgerd","sequence":"additional","affiliation":[{"name":"Department of Neurology, BG-University Hospital Bergmannsheil gGmbH, Ruhr-University Bochum, 44789 Bochum, Germany"},{"name":"Heimer Institute for Muscle Research, BG-University Hospital Bergmannsheil gGmbH, Ruhr-University Bochum, 44789 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1016\/S0140-6736(08)61555-X","article-title":"Pompe\u2019s Disease","volume":"372","author":"Reuser","year":"2008","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1007\/s00415-005-0922-9","article-title":"The Natural Course of Non-Classic Pompe\u2019s Disease; a Review of 225 Published Cases","volume":"252","author":"Winkel","year":"2005","journal-title":"J. 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