title: Two populations of neuronal intranuclear inclusions in SCA7 differ in size and promyelocytic leukaemia protein content.
abstract: Spinocerebellar ataxia type 7 (SCA7) is a hereditary progressive cerebellar ataxia with retinal degeneration associated with an abnormally expanded polyglutamine stretch. Neuronal intranuclear inclusions (NIIs), as in other polyglutamine diseases, are pathological hallmarks of these disorders. NIIs in polyglutamine diseases contain not only the protein with the expanded polyglutamine stretch but also other types of proteins. Several chaperone proteins related to the ubiquitin proteasome pathway, transcription factors and nuclear matrix proteins have been detected in NIIs. The composition of NIIs might reflect the process of NII formation and part of the pathogenesis of these diseases. To investigate how these proteins relate to the pathogenesis of SCA7, we performed immunohistochemical analyses of the composition of NIIs in two cases of SCA7. We demonstrated that there are two types of NIIs in SCA7 that differ in size and immunoreactivity to promyelocytic leukaemia protein (PML), one of the essential components of nuclear bodies (NBs; also called PML oncogenic domains). Small and large NIIs contained ataxin-7, human DnaJ homologue 2 (HDJ-2) and proteasome subunit 19S. In contrast, PML was found only in small NIIs. CREB-binding protein (CBP), another component of NBs, was distributed like PML in NIIs. Our results suggest that NIIs are formed by the accumulation of ataxin-7 in NBs, which become enlarged as they recruit related proteins.
authors.affiliation: Laboratoire de Neuropathologie Raymond Escourolle, Paris, France.
authors.forename: Junko
authors.initials: J
authors.lastname: Takahashi
authors.forename: Hiroto
authors.initials: H
authors.lastname: Fujigasaki
authors.forename: Cecilia
authors.initials: C
authors.lastname: Zander
authors.forename: Khalid H
authors.initials: KH
authors.lastname: El Hachimi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stevanin
authors.forename: Alexandra
authors.initials: A
authors.lastname: Dürr
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Lebre
authors.forename: Gaël
authors.initials: G
authors.lastname: Yvert
authors.forename: Yvon
authors.initials: Y
authors.lastname: Trottier
authors.forename: Hugues
authors.initials: H
authors.lastname: de Thé
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Hauw
authors.forename: Charles
authors.initials: C
authors.lastname: Duyckaerts
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
mesh_terms: D000328:Adult; D000067719:Ataxin-7; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D002648:Child; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D018832:Molecular Chaperones / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D013132:Spinocerebellar Degenerations / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000096:biosynthesis*; D025521:Tumor Suppressor Proteins
chemical_list: C000593829:ATXN7 protein, human; D000067719:Ataxin-7; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human