Ataxin 1 and Ataxin 3 in Neuronal Intranuclear Inclusion Disease

Abstract

Neuronal intranuclear inclusion disease (NIID) is a multisystem neurodegenerative disorder characterized by large intranuclear aggregates in neurons of the central and peripheral nervous system. These ubiquitinated intranuclear inclusions are morphologically similar to the intraneuronal aggregates that have been identified in the CAG/polyglutamine expansion diseases. As rare aggregates in NIID contain a polyglutamine epitope, we further investigated the relationship between this disease and the CAG/polyglutamine expansion diseases. Here, we show that ataxin 1 and ataxin 3 proteins are recruited into aggregates in NIID in the absence of a CAG expansion in the SCA1 and SCA3 genes. These data support an association of NIID with the polyglutamine disorders and provide evidence of in vivo recruitment of proteins with polyglutamine tracts into intraneuronal aggregates.

Neuronal intranuclear inclusion disease: Report on a case originally diagnosed as dopa‐responsive dystonia with Lewy bodies

“…In our case the intranuclear inclusions were not stained with the 1C2 antibody, which recognizes abnormally extended polyglutamine tracts 9, 46, 47. A low proportion of nuclear inclusions stained with the 1C2 antibody have been reported in some other cases of NIID 9, 45, 48. Trinucleotide‐repeat disorders such as SCAs, DRPLA, and HD should be excluded before diagnosing NIID.…”

“…Inclusions have also been noted in male carriers of the fragile X mental retardation (FMR1) premutation that is associated with CGG repeat expansions, but not in individuals with the full mutation 37. Ataxin 1 and ataxin 3, both proteins with long polyglutamine tracts, are present in aggregates in NIID in the absence of CAG expansion in the SCA1 and SCA3 genes 45. This suggests that inclusions may arise as a consequence of a common pathological pathway.…”

Ubiquitin/proteasome pathway impairment in neurodegeneration: therapeutic implications

“…Abnormal expansion to over 53 glutamines is pathological and causes Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 [138]. This neurodegenerative disorder is characterized by ubiquitinated intranuclear inclusions that also contain ataxin-3 [139]. …”

Neuronal intranuclear inclusion disease: Two cases of dopa‐responsive juvenile parkinsonism with drug‐induced dyskinesia

“…First, there is typically an inverse correlation between the inclusion number and the extent of neuronal loss 28. Second, the inclusions are immunopositive for SUMO‐1,29 which is thought to have a protective role against neuronal degradation 30–32. Such inclusions are also found in many degenerative disorders, especially in spinocerebellar ataxias and other polyglutamine diseases 1, 2, 7, 17, 30, 31.…”

“…Such inclusions are also found in many degenerative disorders, especially in spinocerebellar ataxias and other polyglutamine diseases 1, 2, 7, 17, 30, 31. Ataxin 1 and ataxin 3, both proteins with long polyglutamine tracts, are also present in the inclusions of NIID32. Some inclusions in NIID also show immunoreactivity to IC2, a monoclonal antibody that recognizes abnormally expanded polyglutamine.…”