FUS Immunogold Labeling TEM Analysis of the Neuronal Cytoplasmic Inclusions of Neuronal Intermediate Filament Inclusion Disease: A Frontotemporal Lobar Degeneration with FUS Proteinopathy
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- 作者：Tristan Page (1)
Michael A. Gitcho (2)
Sabrina Mosaheb (3)
Deborah Carter (4) (5)
Sumi Chakraverty (4) (6)
Robert H. Perry (7)
Eileen H. Bigio (8) (9)
Marla Gearing (10) (11)
Isidre Ferrer (12)
Alison M. Goate (13) (4) (6)
Nigel J. Cairns (13) (4) (5)
Julian R. Thorpe (1) - 关键词：Neuronal intermediate filament inclusion disease ; Frontotemporal lobar degeneration ; FUS ; Neurofilament ; α ; Internexin ; Immunoelectron microscopy
- 刊名：Journal of Molecular Neuroscience
- 出版年：2011
- 出版时间：November 2011
- 年：2011
- 卷：45
- 期：3
- 页码：409-421
- 全文大小：830KB
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Michael A. Gitcho (2)
Sabrina Mosaheb (3)
Deborah Carter (4) (5)
Sumi Chakraverty (4) (6)
Robert H. Perry (7)
Eileen H. Bigio (8) (9)
Marla Gearing (10) (11)
Isidre Ferrer (12)
Alison M. Goate (13) (4) (6)
Nigel J. Cairns (13) (4) (5)
Julian R. Thorpe (1)
1. Electron Microscope Division, Sussex Centre for Advanced Microscopy, John Maynard-Smith Building, School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9QG, East Sussex, UK
2. Division of Pharmaceutical Sciences, University of Wisconsin, Madison, WI, USA
3. Department of Clinical Biochemistry, Royal Berkshire NHS Foundation Trust, Reading, Berkshire, UK
4. Charles F. and Joanne Knight Alzheimer’s Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA
5. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
6. Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
7. Department of Neuropathology, Newcastle General Hospital, Newcastle-upon-Tyne, UK
8. Cognitive Neurology and Alzheimer Disease Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
9. Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
10. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
11. Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA, USA
12. Institut de Neuropatologia, Idibell-Hospital Universityari de Bellvitge, Universitat de Barcelona, Hospitalet de Llobregat, Spain
13. Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
文摘
Fused in sarcoma (FUS)-immunoreactive neuronal and glial inclusions define a novel molecular pathology called FUS proteinopathy. FUS has been shown to be a component of inclusions of familial amyotrophic lateral sclerosis with FUS mutation and three frontotemporal lobar degeneration entities, including neuronal intermediate filament inclusion disease (NIFID). The pathogenic role of FUS is unknown. In addition to FUS, many neuronal cytoplasmic inclusions (NCI) of NIFID contain aggregates of α-internexin and neurofilament proteins. Herein, we have shown that: (1) FUS becomes relatively insoluble in NIFID and there are no apparent posttranslational modifications, (2) there are no pathogenic abnormalities in the FUS gene in NIFID, and (3) immunoelectron microscopy demonstrates the fine structural localization of FUS in NIFID which has not previously been described. FUS localized to euchromatin, and strongly with paraspeckles, in nuclei, consistent with its RNA/DNA-binding functions. NCI of varying morphologies were observed. Most frequent were the “loosely aggregated cytoplasmic inclusions,-81% of which had moderate or high levels of FUS immunoreactivity. Much rarer “compact cytoplasmic inclusions-and “tangled twine ball inclusions-were FUS-immunoreactive at their granular peripheries, or heavily FUS-positive throughout, respectively. Thus, FUS may aggregate in the cytoplasm and then admix with neuronal intermediate filament accumulations.