{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:05:05Z","timestamp":1791266705117,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2003,11,1]],"date-time":"2003-11-01T00:00:00Z","timestamp":1067644800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001675","name":"International Brain Research Organization","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001675","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008358","name":"Hersenstichting","doi-asserted-by":"publisher","award":["H00.06"],"award-info":[{"award-number":["H00.06"]}],"id":[{"id":"10.13039\/501100008358","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008398","name":"Internationale Stichting Alzheimer Onderzoek","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008398","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2003,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Molecular misreading of the ubiquitin\u2010B (UBB) gene results in a dinucleotide deletion in UBB mRNA. The resulting mutant protein, UBB\n                    <jats:sup>+1<\/jats:sup>\n                    , accumulates in the neuropathological hallmarks of Alzheimer disease. In vitro, UBB\n                    <jats:sup>+1<\/jats:sup>\n                    inhibits proteasomal proteolysis, although it is also an ubiquitin fusion degradation substrate for the proteasome. Using the ligase chain reaction to detect dinucleotide deletions, we report here that UBB\n                    <jats:sup>+1<\/jats:sup>\n                    transcripts are present in each neurodegenerative disease studied (tauo\u2010 and synucleinopathies) and even in control brain samples. In contrast to UBB\n                    <jats:sup>+1<\/jats:sup>\n                    transcripts, UBB\n                    <jats:sup>+1<\/jats:sup>\n                    protein accumulation in the ubiquitin\u2010containing neuropathological hallmarks is restricted to the tauopathies such as Pick disease, frontotemporal dementia, progressive supranuclear palsy, and argyrophilic grain disease. Remarkably, UBB\n                    <jats:sup>+1<\/jats:sup>\n                    protein is not detected in the major forms of synucleinopathies (Lewy body disease and multiple system atrophy). The neurologically intact brain can cope with UBB\n                    <jats:sup>+1<\/jats:sup>\n                    as lentivirally delivered UBB\n                    <jats:sup>+1<\/jats:sup>\n                    protein is rapidly degraded in rat hippocampus, whereas the K29,48R mutant of UBB\n                    <jats:sup>+1<\/jats:sup>\n                    , which is not ubiquitinated, is abundantly expressed. The finding that UBB\n                    <jats:sup>+1<\/jats:sup>\n                    protein only accumulates in tauopathies thus implies that the ubiquitin\u2010proteasome system is impaired specifically in this group of neurodegenerative diseases and not in synucleinopathies and that the presence of UBB\n                    <jats:sup>+1<\/jats:sup>\n                    protein reports proteasomal dysfunction in the brain.\u2014Fischer, D. F., de Vos, R. A. I., van Dijk, R., de Vrij, F. M. S., Proper, E. A., Sonnemans, M. A. F., Verhage, M. C., Sluijs, J. A., Hobo, B., Zouambia, M., Jansen Steur, E. N. H., Kamphorst, W., Hol, E. M., van Leeuwen, F. W. Disease\u2010specific accumulation of mutant ubiquitin as a marker for proteasomal dysfunction in the brain.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    17, 2014\u20132024 (2003)\n                  <\/jats:p>","DOI":"10.1096\/fj.03-0205com","type":"journal-article","created":{"date-parts":[[2003,11,3]],"date-time":"2003-11-03T20:47:39Z","timestamp":1067892459000},"page":"2014-2024","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":122,"title":["Disease\u2010specific accumulation of mutant ubiquitin as a marker for proteasomal dysfunction in the brain"],"prefix":"10.1096","volume":"17","author":[{"given":"David F.","family":"Fischer","sequence":"first","affiliation":[{"name":"Graduate School for Neurosciences Amsterdam Netherlands Institute for Brain Research  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob A. I.","family":"de Vos","sequence":"additional","affiliation":[{"name":"Pathological Laboratory Oost Nederland Medisch Spectrum Twente  Enschede The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renske","family":"van Dijk","sequence":"additional","affiliation":[{"name":"Graduate School for Neurosciences Amsterdam Netherlands Institute for Brain Research  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Femke M. S.","family":"de Vrij","sequence":"additional","affiliation":[{"name":"Graduate School for Neurosciences Amsterdam Netherlands Institute for Brain Research  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelien A.","family":"Proper","sequence":"additional","affiliation":[{"name":"Rudolf Magnus Institute for Neurosciences Utrecht Medical Centre  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc A. F.","family":"Sonnemans","sequence":"additional","affiliation":[{"name":"Graduate School for Neurosciences Amsterdam Netherlands Institute for Brain Research  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian C.","family":"Verhage","sequence":"additional","affiliation":[{"name":"Graduate School for Neurosciences Amsterdam Netherlands Institute for Brain Research  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline A.","family":"Sluijs","sequence":"additional","affiliation":[{"name":"Graduate School for Neurosciences Amsterdam Netherlands Institute for Brain Research  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Hobo","sequence":"additional","affiliation":[{"name":"Graduate School for Neurosciences Amsterdam Netherlands Institute for Brain Research  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Zouambia","sequence":"additional","affiliation":[{"name":"Graduate School for Neurosciences Amsterdam Netherlands Institute for Brain Research  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernst N. 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Jansen","family":"Steur","sequence":"additional","affiliation":[{"name":"Pathological Laboratory Oost Nederland Medisch Spectrum Twente  Enschede The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter","family":"Kamphorst","sequence":"additional","affiliation":[{"name":"Department of Neuropathology University Hospital Free University  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elly M.","family":"Hol","sequence":"additional","affiliation":[{"name":"Graduate School for Neurosciences Amsterdam Netherlands Institute for Brain Research  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred W.","family":"van Leeuwen","sequence":"additional","affiliation":[{"name":"Graduate School for Neurosciences Amsterdam Netherlands Institute for Brain Research  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2001.81.2.741"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.24.1.1121"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8346443"},{"key":"e_1_2_6_5_1","first-page":"343","volume-title":"Neuronal Degeneration and Regeneration: From Basic Mechanisms to Prospects for Therapy","author":"Swaab D. 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