{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:53:04Z","timestamp":1790697184197,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"23-24","license":[{"start":{"date-parts":[[2012,11,22]],"date-time":"2012-11-22T00:00:00Z","timestamp":1353542400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:p>Niemann\u2010<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>ick <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content> disease (<jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content>) is a neurodegenerative lysosomal disorder characterized by storage of cholesterol and other lipids caused by defects in <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content>1, a transmembrane protein involved in cholesterol export from the lysosome, or <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content>2, an intralysosomal cholesterol transport protein. Alterations in lysosomal activities have been implicated in <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content> pathogenesis therefore the aim of this study was to conduct a proteomic analysis of lysosomal proteins in mice deficient in either <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content>1 or <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content>2 to identify secondary changes that might be associated with disease. Lysosomal proteins containing the specific mannose 6\u2010phosphate modification were purified from wild\u2010type and <jats:italic><jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>pc1<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>pc2<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mutant mouse brains at different stages of disease progression and identified by bottom\u2010up <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> and quantified by spectral counting. Levels of a number of lysosomal proteins involved in lipid catabolism including prosaposin and the two subunits of \u03b2\u2010hexosaminidase were increased in both forms of <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content>, possibly representing a compensatory cellular response to the accumulation of glycosphingolipids. Several other lysosomal proteins were significantly altered, including proteases and glycosidases. Changes in lysosomal protein levels corresponded with similar alterations in activities and transcript levels. Understanding the rationale for such changes may provide insights into the pathophysiology of <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content>.<\/jats:p>","DOI":"10.1002\/pmic.201200205","type":"journal-article","created":{"date-parts":[[2012,10,16]],"date-time":"2012-10-16T04:32:05Z","timestamp":1350361925000},"page":"3499-3509","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Proteomic analysis of mouse models of <scp>N<\/scp>iemann\u2010<scp>P<\/scp>ick <scp>C<\/scp> disease reveals alterations in the steady\u2010state levels of lysosomal proteins within the brain"],"prefix":"10.1002","volume":"12","author":[{"given":"David E.","family":"Sleat","sequence":"first","affiliation":[{"name":"Center for Advanced Biotechnology and Medicine University of Medicine and Dentistry of New Jersey Piscataway NJ USA"},{"name":"Department of Biochemistry and Molecular Biology Robert\u2010Wood Johnson Medical School University of Medicine and Dentistry of New Jersey Piscataway NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"Wiseman","sequence":"additional","affiliation":[{"name":"Center for Advanced Biotechnology and Medicine University of Medicine and Dentistry of New Jersey Piscataway NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Istvan","family":"Sohar","sequence":"additional","affiliation":[{"name":"Center for Advanced Biotechnology and Medicine University of Medicine and Dentistry of New Jersey Piscataway NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mukarram","family":"El\u2013Banna","sequence":"additional","affiliation":[{"name":"Center for Advanced Biotechnology and Medicine University of Medicine and Dentistry of New Jersey Piscataway NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Center for Advanced Biotechnology and Medicine University of Medicine and Dentistry of New Jersey Piscataway NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk F.","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University of Medicine and Dentistry of New Jersey Piscataway NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Lobel","sequence":"additional","affiliation":[{"name":"Center for Advanced Biotechnology and Medicine University of Medicine and Dentistry of New Jersey Piscataway NJ USA"},{"name":"Department of Biochemistry and Molecular Biology Robert\u2010Wood Johnson Medical School University of Medicine and Dentistry of New Jersey Piscataway NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,11,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4899-2540-4"},{"key":"e_1_2_7_3_1","volume-title":"The metabolic & molecular bases of inherited disease","author":"Scriver C. R.","year":"2001"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2010.06976.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-5-16"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5323.228"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M707943200"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M707944200"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0405255101"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5500.2298"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2004.06.013"},{"key":"e_1_2_7_12_1","first-page":"86","article-title":"Cholesterol transfer proteins from ram cauda epidydimal and seminal plasma","volume":"48","author":"Baker C. S.","year":"1993","journal-title":"Biol. Reprod. Suppl."},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608743200"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1388-1981(99)00070-0"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M703848200"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0807328105"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.03.049"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2010.05.016"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1022575511354"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(80)90116-2"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M005296200"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2010.01046.x"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023677"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5323.232"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308456101"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr800135v"},{"key":"e_1_2_7_27_1","first-page":"217","article-title":"Using the global proteome machine for protein identification","volume":"328","author":"Beavis R. C.","year":"2006","journal-title":"Methods Mol. Biol."},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr049882h"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac0498563"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr0600273"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M500343-MCP200"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4899-3242-6"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.32.19191"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20080411"},{"key":"e_1_2_7_35_1","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1042\/bj3390743","article-title":"Pig kidney legumain: an asparaginyl endopeptidase with restricted specificity","volume":"339","author":"Dando P. M.","year":"1999","journal-title":"Biochem. J."},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10719-008-9137-5"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.1.207"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(01)00517-6"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5981-10.2011"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.10.018"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3340547"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2008.09.020"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/0885-4505(86)90143-X"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.04709.x"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.9.3493"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/64.4.323"}],"container-title":["PROTEOMICS"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpmic.201200205","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pmic.201200205","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T15:12:11Z","timestamp":1761059531000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/pmic.201200205"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,11,22]]},"references-count":45,"journal-issue":{"issue":"23-24","published-print":{"date-parts":[[2012,12]]}},"alternative-id":["10.1002\/pmic.201200205"],"URL":"https:\/\/doi.org\/10.1002\/pmic.201200205","archive":["Portico"],"relation":{},"ISSN":["1615-9853","1615-9861"],"issn-type":[{"value":"1615-9853","type":"print"},{"value":"1615-9861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,11,22]]},"assertion":[{"value":"2012-05-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-10-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-11-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}