title: Valosin-containing protein immunoreactivity in tauopathies, synucleinopathies, polyglutamine diseases and intranuclear inclusion body disease.
abstract: Valosin-containing protein (VCP) is associated with multiple cellular functions, including ubiquitin-dependent protein degradation. Mutations in VCP are known to cause inclusion body myopathy with Paget's disease and frontotemporal dementia and familial amyotrophic lateral sclerosis (fALS; ALS14), both of which are characterized by trans-activation response DNA protein 43 (TDP-43)-positive neuronal cytoplasmic and nuclear inclusions. Recently, immunoreactivity for fALS-associated proteins (TDP-43, fused in sarcoma (FUS), optineurin and ubiquilin-2) were reported to be present in cytoplasmic and nuclear inclusions in various neurodegenerative diseases. However, the extent and frequency of VCP-immunoreactive structures in these neurodegenerative diseases are uncertain. We immunohistochemically examined the brains of 72 cases with neurodegenerative diseases and five control cases. VCP immunoreactivity was present in Lewy bodies in Parkinson's disease and dementia with Lewy bodies, and neuronal nuclear inclusions in five polyglutamine diseases and intranuclear inclusion body disease, as well as in Marinesco bodies in aged control subjects. However, other neuronal and glial cytoplasmic inclusions in tauopathies and TDP-43 proteinopathies were unstained. These findings suggest that VCP may have common mechanisms in the formation or degradation of cytoplasmic and nuclear inclusions of neurons, but not of glial cells, in several neurodegenerative conditions.
authors.affiliation: Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Mori
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Tanji
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Toyoshima
authors.forename: Hidenao
authors.initials: H
authors.lastname: Sasaki
authors.forename: Mari
authors.initials: M
authors.lastname: Yoshida
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kakita
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Koichi
authors.initials: K
authors.lastname: Wakabayashi
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein
keywords: Lewy body; Marinesco body; neuronal nuclear inclusion; polyglutamine disease; valosin-containing protein