{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T07:49:54Z","timestamp":1791186594238,"version":"4.1.0"},"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2015,4,17]],"date-time":"2015-04-17T00:00:00Z","timestamp":1429228800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Mutations in the valosin containing protein (VCP) gene cause hereditary Inclusion body myopathy (hIBM) associated with Paget disease of bone (PDB), frontotemporal dementia (FTD), more recently termed multisystem proteinopathy (MSP). Affected individuals exhibit scapular winging and die from progressive muscle weakness, and cardiac and respiratory failure, typically in their 40s to 50s. Histologically, patients show the presence of rimmed vacuoles and TAR DNA-binding protein 43 (TDP-43)-positive large ubiquitinated inclusion bodies in the muscles. We have generated a VCP\n                    <jats:sup>R155H\/+<\/jats:sup>\n                    mouse model which recapitulates the disease phenotype and impaired autophagy typically observed in patients with VCP disease. Autophagy-modifying agents, such as rapamycin and chloroquine, at pharmacological doses have previously shown to alter the autophagic flux. Herein, we report results of administration of rapamycin, a specific inhibitor of the mechanistic target of rapamycin (mTOR) signaling pathway, and chloroquine, a lysosomal inhibitor which reverses autophagy by accumulating in lysosomes, responsible for blocking autophagy in 20-month old VCP\n                    <jats:sup>R155H\/+<\/jats:sup>\n                    mice. Rapamycin-treated mice demonstrated significant improvement in muscle performance, quadriceps histological analysis, and rescue of ubiquitin, and TDP-43 pathology and defective autophagy as indicated by decreased protein expression levels of LC3-I\/II, p62\/SQSTM1, optineurin and inhibiting the mTORC1 substrates. Conversely, chloroquine-treated VCP\n                    <jats:sup>R155H\/+<\/jats:sup>\n                    mice revealed progressive muscle weakness, cytoplasmic accumulation of TDP-43, ubiquitin-positive inclusion bodies and increased LC3-I\/II, p62\/SQSTM1, and optineurin expression levels. Our in vitro patient myoblasts studies treated with rapamycin demonstrated an overall improvement in the autophagy markers. Targeting the mTOR pathway ameliorates an increasing list of disorders, and these findings suggest that VCP disease and related neurodegenerative multisystem proteinopathies can now be included as disorders that can potentially be ameliorated by rapalogs.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0122888","type":"journal-article","created":{"date-parts":[[2015,4,17]],"date-time":"2015-04-17T17:06:33Z","timestamp":1429290393000},"page":"e0122888","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":90,"title":["RETRACTED: Rapamycin and Chloroquine: The In Vitro and In Vivo Effects of Autophagy-Modifying Drugs Show Promising Results in Valosin Containing Protein Multisystem Proteinopathy"],"prefix":"10.1371","volume":"10","author":[{"given":"Ang\u00e8le","family":"Nalbandian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina J.","family":"Llewellyn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puya G.","family":"Yazdi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia E.","family":"Kimonis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2015,4,17]]},"reference":[{"issue":"4","key":"pone.0122888.ref001","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1097\/00125817-200007000-00006","article-title":"Clinical and molecular studies in a unique family with autosomal dominant limb-girdle muscular dystrophy and Paget disease of bone","volume":"2","author":"VE Kimonis","year":"2000","journal-title":"Genet Med"},{"issue":"4","key":"pone.0122888.ref002","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1006\/mgme.2001.3256","article-title":"Clinical delineation and localization to chromosome 9p13.3-p12 of a unique dominant disorder in four families: hereditary inclusion body myopathy, Paget disease of bone, and frontotemporal dementia","volume":"74","author":"MJ Kovach","year":"2001","journal-title":"Molecular genetics and metabolism"},{"issue":"7\u20138","key":"pone.0122888.ref003","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/S0960-8966(03)00070-1","article-title":"Clinical and genetic heterogeneity in chromosome 9p associated hereditary inclusion body myopathy: exclusion of GNE and three other candidate genes","volume":"13","author":"GD Watts","year":"2003","journal-title":"Neuromuscul Disord"},{"issue":"4","key":"pone.0122888.ref004","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/ng1332","article-title":"Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein","volume":"36","author":"GD Watts","year":"2004","journal-title":"Nature genetics"},{"issue":"6","key":"pone.0122888.ref005","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1002\/ajmg.a.31862","article-title":"Clinical studies in familial VCP myopathy associated with Paget disease of bone and frontotemporal dementia","volume":"146","author":"VE Kimonis","year":"2008","journal-title":"American journal of medical genetics"},{"key":"pone.0122888.ref006","doi-asserted-by":"crossref","unstructured":"Kimonis VE, Fulchiero E, Vesa J, Watts G. VCP disease associated with myopathy, paget disease of bone and frontotemporal dementia: Review of a unique disorder. Biochimica et biophysica acta. 2008. 18845250.","DOI":"10.1016\/j.bbadis.2008.09.003"},{"key":"pone.0122888.ref007","unstructured":"Kimonis V, Donkervoort S, Watts G. Inclusion Body Myopathy Associated with Paget Disease of Bone and\/or Frontotemporal Dementia Gene [Review]. 2011. 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A Brazilian family with IBMPFD caused by p.R93C mutation in the VCP gene and literature review for genotype-phenotype correlations. Experimental Brain Research\u2014Manuscript ID EBR-10-0487 2011."},{"issue":"6","key":"pone.0122888.ref018","first-page":"787","article-title":"Inclusion body myopathy with Paget disease of bone and frontotemporal dementia linked to VCP p.Arg155Cys in a Korean family","volume":"68","author":"EJ Kim","year":"2011","journal-title":"Archives of neurology"},{"key":"pone.0122888.ref019","doi-asserted-by":"crossref","unstructured":"Komatsu J, Iwasa K, Yanase D, Yamada M. Inclusion body myopathy with Paget disease of the bone and frontotemporal dementia associated with a novel G156S mutation in the VCP gene. 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Lipid-enriched diet rescues lethality and slows down progression in a murine model of VCP-associated disease. Human molecular genetics. 2013. 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Rapamycin: One Drug, Many Effects. Cell Metab. 2014. doi: 10.1016\/j.cmet.2014.01.001 24508508.","DOI":"10.1016\/j.cmet.2014.01.001"},{"issue":"1","key":"pone.0122888.ref050","first-page":"99","article-title":"Metastatic perivascular epithelioid cell tumor responding to mammalian target of rapamycin inhibition. Indian journal of medical and paediatric oncology: official journal of Indian Society of Medical &","volume":"35","author":"I Ghosh","year":"2014","journal-title":"Paediatric Oncology"},{"key":"pone.0122888.ref051","doi-asserted-by":"crossref","unstructured":"Muzic JG, Kindle SA, Tollefson MM. Successful Treatment of Subungual Fibromas of Tuberous Sclerosis With Topical Rapamycin. JAMA dermatology. 2014. doi: 10.1001\/jamadermatol.2014.87 24919623.","DOI":"10.1001\/jamadermatol.2014.87"},{"key":"pone.0122888.ref052","doi-asserted-by":"crossref","unstructured":"Peng ZF, Yang L, Wang TT, Han P, Liu ZH, Wei Q. Efficacy and safety of sirolimus for renal angiomyolipoma in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis: a systematic review. The Journal of urology. 2014. doi: 10.1016\/j.juro.2014.04.096 24813310.","DOI":"10.1016\/j.juro.2014.04.096"},{"issue":"8","key":"pone.0122888.ref053","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/nrn3068","article-title":"Fighting neurodegeneration with rapamycin: mechanistic insights","volume":"12","author":"J Bove","year":"2011","journal-title":"Nature reviews Neuroscience"},{"issue":"23","key":"pone.0122888.ref054","doi-asserted-by":"crossref","first-page":"7988","DOI":"10.1523\/JNEUROSCI.0777-14.2014","article-title":"Genetic reduction of mammalian target of rapamycin ameliorates Alzheimer's disease-like cognitive and pathological deficits by restoring hippocampal gene expression signature","volume":"34","author":"A Caccamo","year":"2014","journal-title":"J Neurosci"},{"key":"pone.0122888.ref055","doi-asserted-by":"crossref","first-page":"e418","DOI":"10.1038\/cddis.2012.159","article-title":"Autophagy as a new therapeutic target in Duchenne muscular dystrophy","volume":"3","author":"C De Palma","year":"2012","journal-title":"Cell Death Dis"},{"issue":"6165","key":"pone.0122888.ref056","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1126\/science.1244360","article-title":"mTOR inhibition alleviates mitochondrial disease in a mouse model of Leigh syndrome","volume":"342","author":"SC Johnson","year":"2013","journal-title":"Science"},{"issue":"7253","key":"pone.0122888.ref057","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/nature08221","article-title":"Rapamycin fed late in life extends lifespan in genetically heterogeneous mice","volume":"460","author":"DE Harrison","year":"2009","journal-title":"Nature"},{"issue":"5751","key":"pone.0122888.ref058","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1126\/science.1115535","article-title":"Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients","volume":"310","author":"M Kaeberlein","year":"2005","journal-title":"Science"},{"issue":"2","key":"pone.0122888.ref059","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1101\/gad.1381406","article-title":"Extension of chronological life span in yeast by decreased TOR pathway signaling","volume":"20","author":"RW Powers","year":"2006","journal-title":"Genes & development"},{"issue":"6967","key":"pone.0122888.ref060","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1038\/426620a","article-title":"Genetics: influence of TOR kinase on lifespan in C. elegans","volume":"426","author":"T Vellai","year":"2003","journal-title":"Nature"},{"issue":"2","key":"pone.0122888.ref061","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1002\/mus.23522","article-title":"A progressive translational mouse model of human valosin-containing protein disease: the VCP(R155H\/+) mouse","volume":"47","author":"A Nalbandian","year":"2013","journal-title":"Muscle & 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