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Mutations of the<jats:styled-content style=\"fixed-case\">SIGMAR1<\/jats:styled-content>gene are implicated in the pathogenesis of familial frontotemporal lobar degeneration and motor neuron disease. Involvement of<jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content>dysfunction in the formation of inclusion bodies in various neurodegenerative diseases has also become evident. We performed immunohistochemical staining to clarify the localization of<jats:styled-content style=\"fixed-case\">SIGMAR1<\/jats:styled-content>in the brains of patients with neurodegenerative disorders, including trans\u2010activation response DNA protein 43 (<jats:styled-content style=\"fixed-case\">TDP<\/jats:styled-content>\u201043) proteinopathy, tauopathy, \u03b1\u2010synucleinopathy, polyglutamine disease and intranuclear inclusion body disease (<jats:styled-content style=\"fixed-case\">INIBD<\/jats:styled-content>). Double\u2010immunocytofluorescence and Western blot analyses of cultured cells were also performed to investigate the role of<jats:styled-content style=\"fixed-case\">SIGMAR1<\/jats:styled-content>using a specific exportin 1 inhibitor, leptomycin<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>and an<jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content>stress inducer, thapsigargin.<jats:styled-content style=\"fixed-case\">SIGMAR1<\/jats:styled-content>was consistently shown to be co\u2010localized with neuronal nuclear inclusions in<jats:styled-content style=\"fixed-case\">TDP<\/jats:styled-content>\u201043 proteinopathy, five polyglutamine diseases and<jats:styled-content style=\"fixed-case\">INIBD<\/jats:styled-content>, as well as in intranuclear Marinesco bodies in aged normal controls. Cytoplasmic inclusions in neurons and glial cells were unreactive for<jats:styled-content style=\"fixed-case\">SIGMAR1<\/jats:styled-content>. In cultured cells, immunocytofluorescent study showed that leptomycin<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>and thapsigargin were shown to sequester<jats:styled-content style=\"fixed-case\">SIGMAR1<\/jats:styled-content>within the nucleus, acting together with p62. This finding was also supported by immunoblot analysis. These results indicate that<jats:styled-content style=\"fixed-case\">SIGMAR1<\/jats:styled-content>might shuttle between the nucleus and the cytoplasm. Neurodegenerative diseases characterized by neuronal nuclear inclusions might utilize the<jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content>\u2010related degradation machinery as a common pathway for the degradation of aberrant proteins.<\/jats:p>","DOI":"10.1111\/neup.12080","type":"journal-article","created":{"date-parts":[[2013,12,9]],"date-time":"2013-12-09T09:45:04Z","timestamp":1386582304000},"page":"148-158","source":"Crossref","is-referenced-by-count":61,"title":["Accumulation of the sigma\u20101 receptor is common to neuronal nuclear inclusions in various neurodegenerative diseases"],"prefix":"10.1111","volume":"34","author":[{"given":"Yasuo","family":"Miki","sequence":"first","affiliation":[{"name":"Department of Neuropathology Institute of Brain Science Hirosaki University Graduate School of Medicine Hirosaki 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