{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T02:58:52Z","timestamp":1787626732888,"version":"build-2736575974"},"reference-count":165,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T00:00:00Z","timestamp":1760227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013043","name":"Ariel University Research and Development Department","doi-asserted-by":"publisher","award":["RA2000000457"],"award-info":[{"award-number":["RA2000000457"]}],"id":[{"id":"10.13039\/501100013043","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Skeletal muscle pathologies, including sarcopenia, inflammatory myopathies, and various muscular dystrophies, are strongly influenced by chronic low-grade inflammation and impaired proteostasis. Immunoproteasomes (IMPs), inducible proteolytic complexes activated by pro-inflammatory cytokines, are emerging as regulators linking immune signaling to protein quality control. Evidence suggests that IMPs have paradoxical, context-dependent roles in skeletal muscle. On one hand, they can support proteostasis and muscle regeneration under stress; on the other, persistent activation may sustain cytokine production, antigen presentation, and maladaptive immune\u2013muscle interactions, promoting chronic inflammation and muscle wasting. Selective IMP inhibitors, such as ONX 0914 and KZR-616, display potent anti-inflammatory effects in preclinical models of autoimmune myositis and muscle atrophy. Yet, their use in skeletal muscle pathologies is controversial; while inhibition may dampen harmful immune activation, it could also impair muscle repair and proteostasis. This review summarizes current findings, highlights key contradictions, and explores unresolved questions about the role of IMPs in skeletal muscle pathologies. We emphasize the need for a deeper understanding of IMP-mediated mechanisms in skeletal muscle pathology and strategies combining selective inhibitors to enhance therapeutic efficacy while minimizing adverse effects. IMPs thus represent both a promising and potentially risky therapeutic target, with outcomes highly dependent on disease context.<\/jats:p>","DOI":"10.3390\/cells14201586","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:13:27Z","timestamp":1760361207000},"page":"1586","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Immunoproteasomes in Skeletal Muscle Pathologies: Emerging Roles, Conflicting Evidence, and Future Directions"],"prefix":"10.3390","volume":"14","author":[{"given":"Alexander","family":"Kalinkovich","sequence":"first","affiliation":[{"name":"Department of Anatomy and Anthropology, Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel Aviv 6927846, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3766-7493","authenticated-orcid":false,"given":"Gregory","family":"Livshits","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Anthropology, Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel Aviv 6927846, Israel"},{"name":"Department of Morphological Sciences, Adelson School of Medicine, Ariel University, Ariel 4077625, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s40200-017-0302-x","article-title":"Prevalence of sarcopenia in the world: A systematic review and meta- analysis of general population studies","volume":"16","author":"Shafiee","year":"2017","journal-title":"J. Diabetes Metab. Disord."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"afac220","DOI":"10.1093\/ageing\/afac220","article-title":"Sarcopenia definition, diagnosis and treatment: Consensus is growing","volume":"51","author":"Sayer","year":"2022","journal-title":"Age Ageing"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101883","DOI":"10.1016\/j.arr.2023.101883","article-title":"An elusive consensus definition of sarcopenia impedes research and clinical treatment: A narrative review","volume":"86","author":"Coletta","year":"2023","journal-title":"Ageing Res. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Bilski, J., Pierzchalski, P., Szczepanik, M., Bonior, J., and Zoladz, J.A. (2022). Multifactorial Mechanism of Sarcopenia and Sarcopenic Obesity. Role of Physical Exercise, Microbiota and Myokines. Cells, 11.","DOI":"10.3390\/cells11010160"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.arr.2016.09.008","article-title":"Sarcopenic obesity or obese sarcopenia: A cross talk between age-associated adipose tissue and skeletal muscle inflammation as a main mechanism of the pathogenesis","volume":"35","author":"Kalinkovich","year":"2017","journal-title":"Ageing Res. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"100980","DOI":"10.1016\/j.arr.2019.100980","article-title":"Inflammaging as a common ground for the development and maintenance of sarcopenia, obesity, cardiomyopathy and dysbiosis","volume":"56","author":"Livshits","year":"2019","journal-title":"Ageing Res. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"111931","DOI":"10.1016\/j.exger.2022.111931","article-title":"Inflammaging: The ground for sarcopenia?","volume":"168","author":"Liang","year":"2022","journal-title":"Exp. Gerontol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Antu\u00f1a, E., Cach\u00e1n-Vega, C., Bermejo-Millo, J.C., Potes, Y., Caballero, B., Vega-Naredo, I., Coto-Montes, A., and Garcia-Gonzalez, C. (2022). Inflammaging: Implications in Sarcopenia. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232315039"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Jimenez-Gutierrez, G.E., Mart\u00ednez-G\u00f3mez, L.E., Mart\u00ednez-Armenta, C., Pineda, C., Mart\u00ednez-Nava, G.A., and Lopez-Reyes, A. (2022). Molecular Mechanisms of Inflammation in Sarcopenia: Diagnosis and Therapeutic Update. Cells, 11.","DOI":"10.3390\/cells11152359"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Sun, C., Shen, L., Zhang, Z., and Xie, X. (2020). Therapeutic Strategies for Duchenne Muscular Dystrophy: An Update. Genes, 11.","DOI":"10.3390\/genes11080837"},{"key":"ref_11","first-page":"199","article-title":"Idiopathic inflammatory myopathies: One year in review 2022","volume":"41","author":"Dourado","year":"2023","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1007\/s12272-021-01349-z","article-title":"Understanding of sarcopenia: From definition to therapeutic strategies","volume":"44","author":"Kim","year":"2021","journal-title":"Arch. Pharmacal Res."},{"key":"ref_13","first-page":"174","article-title":"An update on nutrient modulation in the management of disease-induced muscle wasting: Evidence from human studies","volume":"23","author":"Brook","year":"2020","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1242\/dmm.010389","article-title":"Cellular and molecular mechanisms of muscle atrophy","volume":"6","author":"Bonaldo","year":"2013","journal-title":"Dis. Model. Mech."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/nrm3741","article-title":"Regulated protein turnover: Snapshots of the proteasome in action","volume":"15","author":"Bhattacharyya","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.sbi.2019.10.004","article-title":"Understanding the 26S proteasome molecular machine from a structural and conformational dynamics perspective","volume":"61","author":"Greene","year":"2020","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Sahu, I., and Glickman, M.H. (2021). Structural Insights into Substrate Recognition and Processing by the 20S Proteasome. Biomolecules, 11.","DOI":"10.20944\/preprints202101.0026.v1"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.semcdb.2023.08.002","article-title":"Proteotoxic stress and the ubiquitin proteasome system","volume":"156","author":"Kandel","year":"2024","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1093\/oxfordjournals.jbchem.a124327","article-title":"Interferon-gamma induces different subunit organizations and functional diversity of proteasomes","volume":"115","author":"Aki","year":"1994","journal-title":"J. Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1084\/jem.187.1.97","article-title":"Immunoproteasome assembly: Cooperative incorporation of interferon gamma (IFN-gamma)-inducible subunits","volume":"187","author":"Griffin","year":"1998","journal-title":"J. Exp. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/nri2687","article-title":"Proteasomes in immune cells: More than peptide producers?","volume":"10","author":"Groettrup","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"van den Eshof, B.L., Medfai, L., Nolfi, E., Wawrzyniuk, M., and Sijts, A.J.A.M. (2021). The Function of Immunoproteasomes-An Immunologists\u2019 Perspective. Cells, 10.","DOI":"10.3390\/cells10123360"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Basler, M., and Groettrup, M. (2021). On the Role of the Immunoproteasome in Protein Homeostasis. Cells, 10.","DOI":"10.3390\/cells10113216"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.abb.2003.10.010","article-title":"Altered proteasome function and subunit composition in aged muscle","volume":"421","author":"Husom","year":"2004","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1128\/MCB.00622-13","article-title":"Identification of the immunoproteasome as a novel regulator of skeletal muscle differentiation","volume":"34","author":"Cui","year":"2014","journal-title":"Mol. Cell. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"C1716","DOI":"10.1152\/ajpcell.00965.2024","article-title":"Immunoproteasome subunit PSMB8 promotes skeletal muscle regeneration by regulating macrophage phenotyping switch in mice","volume":"328","author":"Zhang","year":"2025","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1038\/s41419-022-05416-1","article-title":"Inhibition of the immunoproteasome modulates innate immunity to ameliorate muscle pathology of dysferlin-deficient BlAJ mice","volume":"13","author":"Farini","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e115","DOI":"10.1016\/S2665-9913(23)00322-3","article-title":"Idiopathic inflammatory myopathies: Current insights and future frontiers","volume":"6","author":"Connolly","year":"2024","journal-title":"Lancet Rheumatol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ghannam, K., Martinez-Gamboa, L., Spengler, L., Krause, S., Smiljanovic, B., Bonin, M., Bhattarai, S., Gr\u00fctzkau, A., Burmester, G.-R., and H\u00e4upl, T. (2014). Upregulation of immunoproteasome subunits in myositis indicates active inflammation with involvement of antigen presenting cells, CD8 T-cells and IFN\u0393. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0104048"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1002\/eji.202249851","article-title":"Effective therapy of polymyositis in mice via selective inhibition of the immunoproteasome","volume":"52","author":"Kirk","year":"2022","journal-title":"Eur. J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1186\/1471-2091-8-S1-S3","article-title":"Role of proteasomes in disease","volume":"8","author":"Dahlmann","year":"2007","journal-title":"BMC Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1038\/s41580-018-0040-z","article-title":"Regulation of proteasome assembly and activity in health and disease","volume":"19","author":"Rousseau","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1124\/pr.117.015370","article-title":"A Practical Review of Proteasome Pharmacology","volume":"71","author":"Thibaudeau","year":"2019","journal-title":"Pharmacol. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"McCarthy, M.K., and Weinberg, J.B. (2015). The immunoproteasome and viral infection: A complex regulator of inflammation. Front. Microbiol., 6.","DOI":"10.3389\/fmicb.2015.00021"},{"key":"ref_35","first-page":"S74","article-title":"The immunoproteasome: A novel drug target for autoimmune diseases","volume":"33","author":"Basler","year":"2015","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s41232-016-0011-8","article-title":"Dysfunctional immunoproteasomes in autoinflammatory diseases","volume":"36","author":"Arimochi","year":"2016","journal-title":"Inflamm. Regen."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.2174\/0929867323666160318173706","article-title":"Immunoproteasome-Selective Inhibitors: A Promising Strategy to Treat Hematologic Malignancies, Autoimmune and Inflammatory Diseases","volume":"23","author":"Ettari","year":"2016","journal-title":"Curr. Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1021\/acschemneuro.4c00099","article-title":"Targeting Microglial Immunoproteasome: A Novel Approach in Neuroinflammatory-Related Disorders","volume":"15","author":"Malek","year":"2024","journal-title":"ACS Chem. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/978-3-030-38266-7_3","article-title":"The Proteasome System in Health and Disease","volume":"1233","author":"Coux","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.cell.2017.04.023","article-title":"The Logic of the 26S Proteasome","volume":"169","author":"Collins","year":"2017","journal-title":"Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1146\/annurev-biochem-062917-011931","article-title":"Structure and Function of the 26S Proteasome","volume":"87","author":"Bard","year":"2018","journal-title":"Annu Rev Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4037","DOI":"10.1002\/(SICI)1521-4141(199912)29:12<4037::AID-IMMU4037>3.0.CO;2-T","article-title":"Dendritic cells up-regulate immunoproteasomes and the proteasome regulator PA28 during maturation","volume":"29","author":"Macagno","year":"1999","journal-title":"Eur. J. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3006","DOI":"10.1172\/JCI29832","article-title":"Virus-induced type I IFN stimulates generation of immunoproteasomes at the site of infection","volume":"116","author":"Shin","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s12013-011-9182-8","article-title":"LPS-induced formation of immunoproteasomes: TNF-\u03b1 and nitric oxide production are regulated by altered composition of proteasome-active sites","volume":"60","author":"Reis","year":"2011","journal-title":"Cell Biochem Biophys."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/B978-0-12-397863-9.00006-7","article-title":"Degradation of damaged proteins: The main function of the 20S proteasome","volume":"109","author":"Pickering","year":"2012","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1126\/science.8066463","article-title":"MHC class I expression in mice lacking the proteasome subunit LMP-7","volume":"265","author":"Fehling","year":"1994","journal-title":"Science"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6665","DOI":"10.4049\/jimmunol.176.11.6665","article-title":"An altered T cell repertoire in MECL-1-deficient mice","volume":"176","author":"Basler","year":"2006","journal-title":"J. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/1074-7613(94)90043-4","article-title":"Altered peptidase and viral-specific T cell response in LMP2 mutant mice","volume":"1","author":"Eichelberger","year":"1994","journal-title":"Immunity"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.coi.2012.01.005","article-title":"Immunoproteasomes at the interface of innate and adaptive immune responses: Two faces of one enzyme","volume":"24","author":"Kloetzel","year":"2012","journal-title":"Curr. Opin. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"9241","DOI":"10.1073\/pnas.0501711102","article-title":"IFN-gamma-induced immune adaptation of the proteasome system is an accelerated and transient response","volume":"102","author":"Heink","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1038\/emboj.2008.148","article-title":"Dissecting beta-ring assembly pathway of the mammalian 20S proteasome","volume":"27","author":"Hirano","year":"2008","journal-title":"EMBO J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"6153","DOI":"10.1074\/jbc.M209292200","article-title":"Beta 2 subunit propeptides influence cooperative proteasome assembly","volume":"278","author":"De","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"24156","DOI":"10.1074\/jbc.M001742200","article-title":"Novel propeptide function in 20 S proteasome assembly influences beta subunit composition","volume":"275","author":"Kingsbury","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Habib, J.A., Lesenfants, J., Vigneron, N., and Van den Eynde, B.J. (2022). Functional Differences between Proteasome Subtypes. Cells, 11.","DOI":"10.3390\/cells11030421"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.cell.2010.07.036","article-title":"Immunoproteasomes preserve protein homeostasis upon interferon-induced oxidative stress","volume":"142","author":"Seifert","year":"2010","journal-title":"Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1016\/j.cell.2013.01.037","article-title":"Immuno- and constitutive proteasomes do not differ in their abilities to degrade ubiquitinated proteins","volume":"152","author":"Nathan","year":"2013","journal-title":"Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e2350613","DOI":"10.1002\/eji.202350613","article-title":"Proteasome composition in immune cells implies special immune-cell-specific immunoproteasome function","volume":"54","author":"Inholz","year":"2024","journal-title":"Eur. J. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3439","DOI":"10.1002\/eji.201040620","article-title":"Immunoproteasomes are essential for survival and expansion of T cells in virus-infected mice","volume":"40","author":"Moebius","year":"2010","journal-title":"Eur. J. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4075","DOI":"10.4049\/jimmunol.176.7.4075","article-title":"T cells lacking immunoproteasome subunits MECL-1 and LMP7 hyperproliferate in response to polyclonal mitogens","volume":"176","author":"Caudill","year":"2006","journal-title":"J. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4182","DOI":"10.4049\/jimmunol.1201183","article-title":"Immunoproteasome subunit LMP7 deficiency and inhibition suppresses Th1 and Th17 but enhances regulatory T cell differentiation","volume":"189","author":"Kalim","year":"2012","journal-title":"J. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"50447","DOI":"10.18632\/oncotarget.14579","article-title":"Prevention of colitis-associated cancer by selective targeting of immunoproteasome subunit LMP7","volume":"8","author":"Vachharajani","year":"2017","journal-title":"Oncotarget"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Oliveri, F., Mink, D., Muchamuel, T., and Basler, M. (2025). Immunoproteasome Inhibition Impairs Differentiation but Not Survival of T Helper 17 Cells. Cells, 14.","DOI":"10.3390\/cells14100689"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1038\/cdd.2016.3","article-title":"Immunoproteasome dysfunction augments alternative polarization of alveolar macrophages","volume":"23","author":"Chen","year":"2016","journal-title":"Cell Death Differ."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1002\/path.5368","article-title":"Immunoproteasome subunit \u03b25i regulates diet-induced atherosclerosis through altering MERTK-mediated efferocytosis in Apoe knockout mice","volume":"250","author":"Liao","year":"2020","journal-title":"J. Pathol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5549","DOI":"10.4049\/jimmunol.1001517","article-title":"Reduced immunoproteasome formation and accumulation of immunoproteasomal precursors in the brains of lymphocytic choriomeningitis virus-infected mice","volume":"185","author":"Kremer","year":"2010","journal-title":"J. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1002\/eji.201545578","article-title":"Inhibition and deficiency of the immunoproteasome subunit LMP7 attenuates LCMV-induced meningitis","volume":"46","author":"Mundt","year":"2016","journal-title":"Eur. J. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s00251-018-1084-0","article-title":"On the role of the immunoproteasome in transplant rejection","volume":"71","author":"Basler","year":"2019","journal-title":"Immunogenetics"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Keller, I.E., Vosyka, O., Takenaka, S., Klo\u00df, A., Dahlmann, B., Willems, L.I., Verdoes, M., Overkleeft, H.S., Marcos, E., and Adnot, S. (2015). Regulation of immunoproteasome function in the lung. Sci. Rep., 5.","DOI":"10.1038\/srep10230"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1164\/rccm.201506-1122OC","article-title":"Impairment of Immunoproteasome Function by Cigarette Smoke and in Chronic Obstructive Pulmonary Disease","volume":"193","author":"Kammerl","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1186\/s12967-021-02965-5","article-title":"HLA-dependent heterogeneity and macrophage immunoproteasome activation during lung COVID-19 disease","volume":"19","author":"Desterke","year":"2021","journal-title":"J. Transl. Med."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Davidson, K., and Pickering, A.M. (2023). The proteasome: A key modulator of nervous system function, brain aging, and neurodegenerative disease. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1124907"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Church, T.R., and Margolis, S.S. (2025). Mechanisms of ubiquitin-independent proteasomal degradation and their roles in age-related neurodegenerative disease. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1531797"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"107215","DOI":"10.1016\/j.phrs.2024.107215","article-title":"The role of the immunoproteasome in cardiovascular disease","volume":"204","author":"Nie","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.freeradbiomed.2024.03.026","article-title":"Mapping the interplay of immunoproteasome and autophagy in different heart failure phenotypes","volume":"218","author":"Ott","year":"2024","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"111646","DOI":"10.1016\/j.ejmech.2019.111646","article-title":"Immunoproteasome-selective inhibitors: An overview of recent developments as potential drugs for hematologic malignancies and autoimmune diseases","volume":"182","author":"Xi","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Abramson, H.N. (2023). Immunotherapy of Multiple Myeloma: Current Status as Prologue to the Future. Int. J. Mol. Sci., 24.","DOI":"10.20944\/preprints202309.1180.v1"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2734","DOI":"10.1158\/1078-0432.CCR-10-1950","article-title":"Nonproteasomal targets of the proteasome inhibitors bortezomib and carfilzomib: A link to clinical adverse events","volume":"17","author":"Anderl","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/nm.1978","article-title":"A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis","volume":"15","author":"Muchamuel","year":"2009","journal-title":"Nat. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.cell.2011.12.030","article-title":"Immuno- and constitutive proteasome crystal structures reveal differences in substrate and inhibitor specificity","volume":"148","author":"Huber","year":"2012","journal-title":"Cell"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Kisselev, A.F. (2021). Site-Specific Proteasome Inhibitors. Biomolecules, 12.","DOI":"10.3390\/biom12010054"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Muchamuel, T., Fan, R.A., Anderl, J.L., Bomba, D.J., Johnson, H.W.B., Lowe, E., Tuch, B.B., McMinn, D.L., Millare, B., and Kirk, C.J. (2023). Zetomipzomib (KZR-616) attenuates lupus in mice via modulation of innate and adaptive immune responses. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1043680"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"10230","DOI":"10.1021\/acs.jmedchem.1c00604","article-title":"Structure-Based Optimization and Discovery of M3258, a Specific Inhibitor of the Immunoproteasome Subunit LMP7 (\u03b25i)","volume":"64","author":"Klein","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_83","first-page":"E8425","article-title":"Brief treatment with a highly selective immunoproteasome inhibitor promotes long-term cardiac allograft acceptance in mice","volume":"113","author":"Karreci","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4667","DOI":"10.1182\/blood-2008-07-171637","article-title":"Targeted inhibition of the immunoproteasome is a potent strategy against models of multiple myeloma that overcomes resistance to conventional drugs and nonspecific proteasome inhibitors","volume":"113","author":"Kuhn","year":"2009","journal-title":"Blood"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1021\/acs.jmedchem.8b01884","article-title":"Structure-Based Design of Inhibitors Selective for Human Proteasome \u03b22c or \u03b22i Subunits","volume":"62","author":"Xin","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.yjmcc.2015.07.027","article-title":"The mammalian target of rapamycin modulates the immunoproteasome system in the heart","volume":"86","author":"Zhang","year":"2015","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.redox.2018.10.021","article-title":"Resveratrol as a new inhibitor of immunoproteasome prevents PTEN degradation and attenuates cardiac hypertrophy after pressure overload","volume":"20","author":"Chen","year":"2019","journal-title":"Redox Biol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Tripathi, S.C., Vedpathak, D., and Ostrin, E.J. (2021). The Functional and Mechanistic Roles of Immunoproteasome Subunits in Cancer. Cells, 10.","DOI":"10.3390\/cells10123587"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Huber, E.M., and Groll, M. (2021). A Nut for Every Bolt: Subunit-Selective Inhibitors of the Immunoproteasome and Their Therapeutic Potential. Cells, 10.","DOI":"10.3390\/cells10081929"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Mancuso, F., Di Chio, C., Di Matteo, F., Smaldone, G., Iraci, N., and Giofr\u00e8, S.V. (2025). Recent Advances in the Development of Immunoproteasome Inhibitors as Anti-Cancer Agents: The Past 5 Years. Molecules, 30.","DOI":"10.3390\/molecules30030755"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1159\/000545170","article-title":"Alzheimer\u2019s Disease, \u03b2-Amyloid Peptides, and Ubiquitin-Proteasome System: Nutritherapeutic Insights","volume":"25","author":"Simon","year":"2025","journal-title":"Neurodegener. Dis."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.coi.2003.11.004","article-title":"Proteasome and peptidase function in MHC-class-I-mediated antigen presentation","volume":"16","author":"Kloetzel","year":"2004","journal-title":"Curr. Opin. Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1111\/jcmm.17104","article-title":"Immunoproteasome modulates NLRP3 inflammasome-mediated neuroinflammation under cerebral ischaemia and reperfusion conditions","volume":"26","author":"Chen","year":"2022","journal-title":"J. Cell. Mol. Med."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Lee, Y., Yoon, B., Son, S., Cho, E., Kim, K.B., Choi, E.Y., and Kim, D.E. (2024). Inhibition of Immunoproteasome Attenuates NLRP3 Inflammasome Response by Regulating E3 Ubiquitin Ligase TRIM31. Cells, 13.","DOI":"10.3390\/cells13080675"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/j.1600-065X.2012.01098.x","article-title":"Regulation of NF-\u03baB by ubiquitination and degradation of the I\u03baBs","volume":"246","author":"Kanarek","year":"2012","journal-title":"Immunol. Rev."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.molimm.2017.01.019","article-title":"Immunoproteasome subunit deficiency has no influence on the canonical pathway of NF-\u03baB activation","volume":"83","author":"Bitzer","year":"2017","journal-title":"Mol. Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"32777","DOI":"10.1074\/jbc.M113.480921","article-title":"Long-term incubation with proteasome inhibitors (PIs) induces I\u03baB\u03b1 degradation via the lysosomal pathway in an I\u03baB kinase (IKK)-dependent and IKK-independent manner","volume":"288","author":"Lee","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/s00281-020-00823-y","article-title":"The complex relationship between Immunosenescence and Inflammaging: Special issue on the New Biomedical Perspectives","volume":"42","author":"Franceschi","year":"2020","journal-title":"Semin. Immunopathol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.immuni.2022.03.016","article-title":"Nonresolving inflammation redux","volume":"55","author":"Nathan","year":"2022","journal-title":"Immunity"},{"key":"ref_100","first-page":"268","article-title":"The Immunoproteasome in oxidative stress, aging, and disease","volume":"51","author":"Pomatto","year":"2015","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1002\/art.33333","article-title":"Beneficial effect of novel proteasome inhibitors in murine lupus via dual inhibition of type I interferon and autoantibody-secreting cells","volume":"64","author":"Ichikawa","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Oliva, M.d.R., Mellett, M., and Basler, M. (2022). Immunoproteasome inhibition attenuates experimental psoriasis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1075615"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1161\/ATVBAHA.123.319701","article-title":"Immunoproteasomal Inhibition With ONX-0914 Attenuates Atherosclerosis and Reduces White Adipose Tissue Mass and Metabolic Syndrome in Mice","volume":"44","author":"Schaftenaar","year":"2024","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e002818","DOI":"10.1136\/rmdopen-2022-002818","article-title":"Immunoproteasome subunit \u03b25i promotes perifascicular muscle atrophy in dermatomyositis by upregulating RIG-I","volume":"9","author":"Zhang","year":"2023","journal-title":"RMD Open"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Du, S.H., Xiang, Y.J., Liu, L., Nie, M., Hou, Y., Wang, L., Li, B.B., Xu, M., Teng, Q.L., and Peng, J. (2021). Co-Inhibition of the Immunoproteasome Subunits LMP2 and LMP7 Ameliorates Immune Thrombocytopenia. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.603278"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Chang, H.H., Lin, Y.H., Chen, T.M., Tsai, Y.L., Lai, C.R., Tsai, W.C., Cheng, Y.C., and Chen, Y. (2022). ONX-0914 Induces Apoptosis and Autophagy with p53 Regulation in Human Glioblastoma Cells. Cancers, 14.","DOI":"10.3390\/cancers14225712"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1038\/s41416-022-02129-2","article-title":"Immunoproteasome inhibition prevents progression of castration-resistant prostate cancer","volume":"128","author":"Li","year":"2023","journal-title":"Br. J. Cancer"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1182\/bloodadvances.2018016360","article-title":"An inhibitor of proteasome \u03b22 sites sensitizes myeloma cells to immunoproteasome inhibitors","volume":"2","author":"Daily","year":"2018","journal-title":"Blood Adv."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"3763","DOI":"10.1021\/acs.jmedchem.0c00416","article-title":"LMP2 Inhibitors as a Potential Treatment for Alzheimer\u2019s Disease","volume":"63","author":"Bhattarai","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.4049\/jimmunol.2000951","article-title":"Noncytotoxic Inhibition of the Immunoproteasome Regulates Human Immune Cells In Vitro and Suppresses Cutaneous Inflammation in the Mouse","volume":"206","author":"Kioon","year":"2021","journal-title":"J. Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Xie, X., Lee, J., Manyam, G.C., Pearson, T., Walter-Bausch, G., Friese-Hamim, M., Zhao, S., Jabs, J., Manginelli, A.A., and Piske, N. (2025). LMP7-Specific Inhibitor M3258 Modulates the Tumor Microenvironment of Triple-Negative Breast Cancer and Inflammatory Breast Cancer. Cancers, 17.","DOI":"10.3390\/cancers17111887"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Moallemian, R., Rehman, A.U., Zhao, N., Wang, H., Chen, H., Lin, G., Ma, X., and Yu, J. (2020). Immunoproteasome inhibitor DPLG3 attenuates experimental colitis by restraining NF-\u03baB activation. Biochem. Pharmacol., 177.","DOI":"10.1016\/j.bcp.2020.113964"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1007\/s11357-021-00510-2","article-title":"A neuromuscular perspective of sarcopenia pathogenesis: Deciphering the signaling pathways involved","volume":"44","author":"Ferreira","year":"2022","journal-title":"Geroscience"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Marzetti, E., Calvani, R., Coelho-J\u00fanior, H.J., Landi, F., and Picca, A. (2024). Mitochondrial Quantity and Quality in Age-Related Sarcopenia. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042052"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s13098-023-01022-z","article-title":"Causal relationship between insulin resistance and sarcopenia","volume":"15","author":"Liu","year":"2023","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"109221","DOI":"10.1016\/j.isci.2024.109221","article-title":"Fat infiltration in skeletal muscle: Influential triggers and regulatory mechanism","volume":"27","author":"Wang","year":"2024","journal-title":"iScience"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/bs.acc.2019.07.010","article-title":"Myokines: The endocrine coupling of skeletal muscle and bone","volume":"94","author":"Gomarasca","year":"2020","journal-title":"Adv. Clin. Chem."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Xie, G., Jin, H., Mikhail, H., Pavel, V., Yang, G., Ji, B., Lu, B., and Li, Y. (2023). Autophagy in sarcopenia: Possible mechanisms and novel therapies. Biomed. Pharmacother., 165.","DOI":"10.1016\/j.biopha.2023.115147"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"He, Y., Xie, W., Li, H., Jin, H., Zhang, Y., and Li, Y. (2022). Cellular Senescence in Sarcopenia: Possible Mechanisms and Therapeutic Potential. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.793088"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1007\/s40266-022-00960-z","article-title":"New Horizons in the Treatment of Age-Associated Obesity, Sarcopenia and Osteoporosis","volume":"39","author":"Kalinkovich","year":"2022","journal-title":"Drugs Aging"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.immuni.2021.12.013","article-title":"Inflammation in obesity, diabetes, and related disorders","volume":"55","author":"Rohm","year":"2022","journal-title":"Immunity"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Izzo, A., Massimino, E., Riccardi, G., and Della Pepa, G. (2021). A Narrative Review on Sarcopenia in Type 2 Diabetes Mellitus: Prevalence and Associated Factors. Nutrients, 13.","DOI":"10.3390\/nu13010183"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Losasso, M.R., Parussolo, M.L.C., Silva, A.O., Direito, R., Quesada, K., Detregiachi, C.R.P., Bechara, M.D., M\u00e9ndez-S\u00e1nchez, N., Abenavoli, L., and Ara\u00fajo, A.C. (2025). Unraveling the Metabolic Pathways Between Metabolic-Associated Fatty Liver Disease (MAFLD) and Sarcopenia. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26104673"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.arr.2015.05.001","article-title":"Sarcopenia-The search for emerging biomarkers","volume":"22","author":"Kalinkovich","year":"2015","journal-title":"Ageing Res. Rev."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1152\/physrev.00061.2017","article-title":"Sarcopenia: Aging-Related Loss of Muscle Mass and Function","volume":"99","author":"Larsson","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"156","DOI":"10.3892\/ijmm.2021.4989","article-title":"Pathophysiology and mechanisms of primary sarcopenia (Review)","volume":"48","author":"Nishikawa","year":"2021","journal-title":"Int. J. Mol. Med."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Wu, J., Ding, P., Wu, H., Yang, P., Guo, H., Tian, Y., Meng, L., and Zhao, Q. (2023). Sarcopenia: Molecular regulatory network for loss of muscle mass and function. Front. Nutr., 10.","DOI":"10.3389\/fnut.2023.1037200"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"101270","DOI":"10.1016\/j.mam.2024.101270","article-title":"Frontiers in sarcopenia: Advancements in diagnostics, molecular mechanisms, and therapeutic strategies","volume":"97","author":"Liu","year":"2024","journal-title":"Mol. Asp. Med."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"e146","DOI":"10.3346\/jkms.2022.37.e146","article-title":"A Review of Sarcopenia Pathophysiology, Diagnosis, Treatment and Future Direction","volume":"37","author":"Cho","year":"2022","journal-title":"J. Korean Med. Sci."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"155597","DOI":"10.1016\/j.metabol.2023.155597","article-title":"Current and investigational medications for the treatment of sarcopenia","volume":"149","author":"Rolland","year":"2023","journal-title":"Metabolism"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Najm, A., Niculescu, A.-G., Grumezescu, A.M., and Beuran, M. (2024). Emerging Therapeutic Strategies in Sarcopenia: An Updated Review on Pathogenesis and Treatment Advances. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25084300"},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Rondanelli, M., Nichetti, M., Peroni, G., Faliva, M.A., Naso, M., Gasparri, C., Perna, S., Oberto, L., Di Paolo, E., and Riva, A. (2021). Where to Find Leucine in Food and How to Feed Elderly With Sarcopenia in Order to Counteract Loss of Muscle Mass: Practical Advice. Front. Nutr., 7.","DOI":"10.3389\/fnut.2020.622391"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1002\/jcsm.13225","article-title":"Exercise for sarcopenia in older people: A systematic review and network meta-analysis","volume":"14","author":"Shen","year":"2023","journal-title":"J. Cachex. Sarcopenia Muscle"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/j.clnu.2014.04.007","article-title":"Protein intake and exercise for optimal muscle function with aging: Recommendations from the ESPEN Expert Group","volume":"33","author":"Deutz","year":"2014","journal-title":"Clin. Nutr."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1093\/ajcn\/nqx028","article-title":"Protein leucine content is a determinant of shorter- and longer-term muscle protein synthetic responses at rest and following resistance exercise in healthy older women: A randomized, controlled trial","volume":"107","author":"Devries","year":"2018","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Arnau, F.M., Fonfr\u00eda-Vivas, R., Buigues, C., Castillo, Y., Molina, P., Hoogland, A.J., van Doesburg, F., Pruimboom, L., Fern\u00e1ndez-Garrido, J., and Cauli, O. (2020). Effects of Leucine Administration in Sarcopenia: A Randomized and Placebo-controlled Clinical Trial. Nutrients, 12.","DOI":"10.3390\/nu12040932"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1007\/s00424-016-1933-3","article-title":"Molecular mechanism of sarcopenia and cachexia: Recent research advances","volume":"469","author":"Sakuma","year":"2017","journal-title":"Pflug. Arch."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Haberecht-M\u00fcller, S., Kr\u00fcger, E., and Fielitz, J. (2021). Out of Control: The Role of the Ubiquitin Proteasome System in Skeletal Muscle during Inflammation. Biomolecules, 11.","DOI":"10.3390\/biom11091327"},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Pang, X., Zhang, P., Chen, X., and Liu, W. (2023). Ubiquitin-proteasome pathway in skeletal muscle atrophy. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1289537"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"14914","DOI":"10.1073\/pnas.1106015108","article-title":"Proteasome assembly defect due to a proteasome subunit beta type 8 (PSMB8) mutation causes the autoinflammatory disorder, Nakajo-Nishimura syndrome","volume":"108","author":"Arima","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1111\/nan.12614","article-title":"Myositis with sarcoplasmic inclusions in Nakajo\u2013Nishimura syndrome: A genetic inflammatory myopathy","volume":"46","author":"Ayaki","year":"2020","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Liu, H.M., Ferrington, D.A., Baumann, C.W., and Thompson, L.V. (2016). Denervation-Induced Activation of the Standard Proteasome and Immunoproteasome. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0166831"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s12192-017-0857-y","article-title":"Downhill exercise alters immunoproteasome content in mouse skeletal muscle","volume":"23","author":"Baumann","year":"2018","journal-title":"Cell Stress Chaperon."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"7650","DOI":"10.18632\/aging.204275","article-title":"Senolytic elimination of senescent macrophages restores muscle stem cell function in severely dystrophic muscle","volume":"14","author":"Liu","year":"2022","journal-title":"Aging"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1038\/mt.2016.162","article-title":"Therapeutic Potential of Immunoproteasome Inhibition in Duchenne Muscular Dystrophy","volume":"24","author":"Farini","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Tripodi, L., Molinaro, D., Fortunato, F., Mella, C., Cassani, B., Torrente, Y., and Farini, A. (2022). Immunoproteasome Inhibition Ameliorates Aged Dystrophic Mouse Muscle Environment. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232314657"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.exger.2016.01.008","article-title":"Muscle function and fat content in relation to sarcopenia, obesity and frailty of old age\u2014An overview","volume":"76","author":"Buch","year":"2016","journal-title":"Exp. Gerontol."},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Nishi, H., Higashihara, T., and Inagi, R. (2019). Lipotoxicity in Kidney, Heart, and Skeletal Muscle Dysfunction. Nutrients, 11.","DOI":"10.3390\/nu11071664"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41574-023-00943-z","article-title":"Sarcopenic obesity in older adults: A clinical overview","volume":"20","author":"Prado","year":"2024","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1002\/jcsm.12901","article-title":"Pathogenesis of sarcopenia and the relationship with fat mass: Descriptive review","volume":"13","author":"Li","year":"2022","journal-title":"J. Cachex. Sarcopenia Muscle"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"R67","DOI":"10.1530\/JOE-15-0533","article-title":"Insulin resistance and sarcopenia: Mechanistic links between common co-morbidities","volume":"229","author":"Cleasby","year":"2016","journal-title":"J. Endocrinol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1139\/apnm-2020-0655","article-title":"Obesity-induced alterations to the immunoproteasome: A potential link to intramuscular lipotoxicity","volume":"46","author":"Fletcher","year":"2021","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1139\/apnm-2021-0764","article-title":"Impaired proteostasis in obese skeletal muscle relates to altered immunoproteasome activity","volume":"47","author":"Fletcher","year":"2022","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Kimura, H., Usui, F., Karasawa, T., Kawashima, A., Shirasuna, K., Inoue, Y., Komada, T., Kobayashi, M., Mizushina, Y., and Kasahara, T. (2015). Immunoproteasome subunit LMP7 Deficiency Improves Obesity and Metabolic Disorders. Sci. Rep., 5.","DOI":"10.1038\/srep15883"},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Lelegren, M., Liu, Y., Ross, C., Tardif, S., and Salmon, A.B. (2016). Pharmaceutical inhibition of mTOR in the common marmoset: Effect of rapamycin on regulators of proteostasis in a non-human primate. Pathobiol. Aging Age-Relat. Dis., 6.","DOI":"10.3402\/pba.v6.31793"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.jaut.2016.08.004","article-title":"The immunoproteasomes are key to regulate myokines and MHC class I expression in idiopathic inflammatory myopathies","volume":"75","author":"Bhattarai","year":"2016","journal-title":"J. Autoimmun."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s00401-024-02765-3","article-title":"Anti-Ku + myositis: An acquired inflammatory protein-aggregate myopathy","volume":"148","author":"Holzer","year":"2024","journal-title":"Acta Neuropathol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1080\/15548627.2025.2457925","article-title":"Limiting cap-dependent translation increases 20S proteasomal degradation and protects the proteomic integrity in autophagy-deficient skeletal muscle","volume":"21","author":"Dong","year":"2025","journal-title":"Autophagy"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"4140","DOI":"10.2174\/1381612811319220018","article-title":"Inhibitors of the immunoproteasome: Current status and future directions","volume":"19","author":"Miller","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Kodro\u0144, A., Kowalski, K., Mussulini, B.H.M., Hazir, C., Borrero-Landazabal, M.A., Ngati, S., Wasilewski, M., and Chacinska, A. (2025). Immunoproteasome-specific Subunit Alterations as a Potential Therapeutic Target for Mitochondriopathies. J. Mol. Biol., 437.","DOI":"10.1016\/j.jmb.2025.169229"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"eadu0284","DOI":"10.1126\/sciimmunol.adu0284","article-title":"Dissection of the immune landscape in psoriatic arthritis defines immunoproteasome up-regulation in treatment resistance","volume":"10","author":"Tzemach","year":"2025","journal-title":"Sci. Immunol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/s41435-020-00109-1","article-title":"Recent insights how combined inhibition of immuno\/proteasome subunits enables therapeutic efficacy","volume":"21","author":"Basler","year":"2020","journal-title":"Genes Immun."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"e46512","DOI":"10.15252\/embr.201846512","article-title":"Co-inhibition of immunoproteasome subunits LMP2 and LMP7 is required to block autoimmunity","volume":"19","author":"Basler","year":"2018","journal-title":"Embo Rep."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"11127","DOI":"10.1021\/acs.jmedchem.8b01201","article-title":"Required Immunoproteasome Subunit Inhibition Profile for Anti-Inflammatory Efficacy and Clinical Candidate KZR-616 ((2S,3R)-N-((S)-3-(Cyclopent-1-en-1-yl)-1-((R)-2-methyloxiran-2-yl)-1-oxopropan-2-yl)-3-hydroxy-3-(4-methoxyphenyl)-2-((S)-2-(2-morpholinoacetamido)propanamido)propenamide)","volume":"61","author":"Johnson","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.chembiol.2018.11.007","article-title":"Proteasome Inhibition in Multiple Myeloma: Head-to-Head Comparison of Currently Available Proteasome Inhibitors","volume":"26","author":"Besse","year":"2019","journal-title":"Cell Chem. Biol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/20\/1586\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:46:31Z","timestamp":1760363191000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/20\/1586"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,12]]},"references-count":165,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["cells14201586"],"URL":"https:\/\/doi.org\/10.3390\/cells14201586","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,12]]}}}