Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/9454
Citations
Scopus Web of Science® Altmetric
?
?
Type: Journal article
Title: SUMO-1 marks the nuclear inclusions in familial neuronal intranuclear inclusion disease
Author: Pountney, D.
Huang, Y.
Burns, R.
Haan, E.
Thompson, P.
Blumbergs, P.
Gai, W.
Citation: Experimental Neurology, 2003; 184(1):436-446
Publisher: Academic Press Inc
Issue Date: 2003
ISSN: 0014-4886
1090-2430
Statement of
Responsibility: 
D. L. Pountney, Y. Huang, R. J. Burns, E. Haan, P. D. Thompson, P. C. Blumbergs and W. P. Gai
Abstract: Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder characterized by progressive ataxia and neuronal nuclear inclusions (NIs), similar to the inclusions found in expanded CAG repeat diseases. NIID may be familial or sporadic. The cause of familial NIID is poorly understood, as no CAG expansion has been detected. We examined three cases, from two unrelated families, who had autosomal dominant NIID but normal CAG repeats in genes involved in polyglutamine neurodegenerative diseases. We found that NIs in all three cases were intensely immunopositive for SUMO-1, a protein which covalently conjugates to other proteins and targets them to the nuclear regions (nuclear bodies) responsible for nuclear proteasomal degradation. Electron microscopy demonstrated that SUMO-1 was located on the 10-nm fibrils of NIs. In cultured PC12 cells, we found that inhibition of proteasome function by specific inhibitors resulted in the appearance of SUMO-1-immunopositive nuclear inclusions. Our study suggests that recruitment of SUMO-1 modified proteins into insoluble nuclear inclusions and proteasomal dysfunction may be involved in the pathogenesis of NIs in familial NIID cases.
Keywords: Brain; PC12 Cells; Inclusion Bodies; Cell Nucleus; Animals; Humans; Rats; Neurodegenerative Diseases; Multienzyme Complexes; Proteasome Endopeptidase Complex; Cysteine Endopeptidases; SUMO-1 Protein; Microscopy, Electron; Blotting, Western; Electrophoresis, Polyacrylamide Gel; Immunohistochemistry; Pedigree; Adult; Aged; Middle Aged; Female; Biomarkers
Description: Copyright © 2003 Elsevier Inc. All rights reserved.
RMID: 0020031372
DOI: 10.1016/j.expneurol.2003.07.004
Appears in Collections:Medicine publications

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.