?-Internexin aggregates are abundant in neuronal intermediate filament inclusion disease (NIFID) but rare in other neurodegenerative diseases

Cairns, Nigel J.; Uryu, Kunihiro; Bigio, Eileen H.; Mackenzie, Ian R.; Gearing, Marla; Duyckaerts, Charles; Yokoo, Hideaki; Nakazato, Yoichi; Jaros, Evelyn; Perry, Robert H.; Arnold, Steven E.; Lee, Virginia M.‐Y.; Trojanowski, John Q.

doi:10.1007/s00401-004-0882-7

Cited by 50 publications

(61 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Generally, the NIIs were more intensely labelled by anti-ubiquitin antibodies than were the cytoplasmic inclusions. Previously, we have shown that some, generally compact, NCIs are only weakly or unstained by ubiquitin IHC [1,6]. With ubiquitin IHC, the NIIs appeared round, sometimes elongated, occasionally occupying more than 50% of the nuclear volume.…”

Section: Niis Of Nifid Are Intensely Ubiquitinatedmentioning

confidence: 74%

“…Antibodies used included those that recognise ubiquitin, expanded polyglutamine repeats, and epitopes of class IV neuronal IF proteins including phosphorylation-dependent and non-phosphorylation-dependent anti-neuronal IF antibodies ( Table 2). Anti-neuronal IF antibodies used in this study are well characterised and have been used previously to demonstrate epitopes of neuronal IFs in NIFID [4,6,7].…”

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

“…Microscopically, there are the stereotypical features of all frontotemporal lobar degenerations (FTLDs): neuronal loss, microvacuolation, and reactive gliosis in affected areas. Abnormal neuronal cytoplasmic aggregates of α-internexin and the three neurofilament (NF) subunits, NF-H, NF-M, and NF-L are the signature lesions of NIFID [1,4,6,7,12,13]. Neuronal cytoplasmic inclusions (NCIs) of NIFID are variably ubiquitinated and, in about half of cases, there are neuronal intranuclear protein inclusions (NIIs), which are also ubiquitinated [4,12,17].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Neuronal intranuclear inclusions are ultrastructurally and immunologically distinct from cytoplasmic inclusions of neuronal intermediate filament inclusion disease

et al. 2005

Self Cite

View full text Add to dashboard Cite

Abnormal neuronal cytoplasmic inclusions (NCIs) containing aggregates of α-internexin and the neurofilament (NF) subunits, NF-H, NF-M, and NF-L, are the signature lesions of neuronal intermediate filament (IF) inclusion disease (NIFID). The disease has a clinically heterogeneous phenotype, including fronto-temporal dementia, pyramidal and extrapyramidal signs presenting at a young age. NCIs are variably ubiquitinated and about half of cases also have neuronal intranuclear inclusions (NIIs), which are also ubiquitinated. NIIs have been described in polyglutamine-repeat expansion diseases, where they are strongly ubiquitin immunoreactive. The fine structure of NIIs of NIFID has not previously been described. Therefore, to determine the ultrastructure of NIIs, immunoelectron microscopy was undertaken on NIFID cases and normal aged control brains. Our results indicate that the NIIs of NIFID are strongly ubiquitin immunoreactive. However, unlike NCIs which contain ubiquitin, α-internexin and NF epitopes, NIIs contain neither epitopes of α-internexin nor NF subunits. Neither NIIs nor NCIs were recognised by antibodies to expanded polyglutamine repeats. The NII of NIFID lacks a limiting membrane and contains straight filaments of 20 nm mean width (range 11-35 nm), while NCIs contain filaments with a mean width of 10 nm (range 5-18 nm; t-test, P<0.001). Biochemistry revealed no differences in neuronal IF protein mobilities between NIFID and normal brain tissue. Therefore, NIIs of NIFID contain filaments morphologically and immunologically distinct from those of NCIs, and both types of inclusion lack expanded polyglutamine tracts of the triplet-repeat expansion diseases. These observations indicate that abnormal protein aggregation follows separate pathways in different neuronal compartments of NIFID.

show abstract

Section: Niis Of Nifid Are Intensely Ubiquitinatedmentioning

confidence: 74%

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Neuronal intranuclear inclusions are ultrastructurally and immunologically distinct from cytoplasmic inclusions of neuronal intermediate filament inclusion disease

et al. 2005

Self Cite

View full text Add to dashboard Cite

show abstract

“…This disease was first described in 2004 in a series of reports by Cairns et al (62,63). Microscopically, this disease is characterized by neuronal IF inclusions that contain neither synuclein nor tau.…”

Section: Neuronal If Inclusion Disease a Recently Described Disease mentioning

confidence: 99%

Dysfunctions of neuronal and glial intermediate filaments in disease

Liem

Messing²

2009

J. Clin. Invest.

125

100

View full text Add to dashboard Cite

Intermediate filaments (IFs) are abundant structures found in most eukaryotic cells, including those in the nervous system. In the CNS, the primary components of neuronal IFs are α-internexin and the neurofilament triplet proteins. In the peripheral nervous system, a fifth neuronal IF protein known as peripherin is also present. IFs in astrocytes are primarily composed of glial fibrillary acidic protein (GFAP), although vimentin is also expressed in immature astrocytes and some mature astrocytes. In this Review, we focus on the IFs of glial cells (primarily GFAP) and neurons as well as their relationship to different neurodegenerative diseases.

show abstract

“…α-Internexin has recently been identified as a major component of the pathological inclusions of the frontotemporal dementia, neuronal intermediate filament inclusion disease (NIFID) (Figure 2). The signature lesion of this disease is the neuronal cytoplasmic inclusion, which is tau-and α-synuclein negative, variably ubiquitinated, and contains epitopes of all type IV IF proteins [59][60][61]. In addition to NFs in swollen axons and spheroids in ALS, peripherin has also been demonstrated by immunohistochemistry (IHC) in the ubiquitinated inclusions of ALS [62].…”

Section: Neuronal Ifs and Diseasementioning

confidence: 99%

The cytoskeleton in neurodegenerative diseases

Cairns

Lee

Trojanowski

2004

The Journal of Pathology

165

114

View full text Add to dashboard Cite

In vitro and transgenic animal models are being used to demonstrate that different mutations impair protein function, promote tau fibrilization, or perturb tau gene splicing, leading to aberrant and distinct tau aggregates. For recognition of these disorders at neuropathological examination, immunohistochemistry is needed, and this may be combined with biochemistry and molecular genetics to properly determine the nosology of a particular case. As reviewed here, the identification of molecular genetic defects and biochemical alterations in cytoskeletal proteins of human neurodegenerative diseases has facilitated experimental studies and will promote the development of assays of molecules which inhibit abnormal neuronal IF and tau protein inclusions.

show abstract

?-Internexin aggregates are abundant in neuronal intermediate filament inclusion disease (NIFID) but rare in other neurodegenerative diseases

Cited by 50 publications

References 32 publications

Neuronal intranuclear inclusions are ultrastructurally and immunologically distinct from cytoplasmic inclusions of neuronal intermediate filament inclusion disease

Neuronal intranuclear inclusions are ultrastructurally and immunologically distinct from cytoplasmic inclusions of neuronal intermediate filament inclusion disease

Dysfunctions of neuronal and glial intermediate filaments in disease

The cytoskeleton in neurodegenerative diseases

Contact Info

Product

Resources

About