Recruitment of nonexpanded polyglutamine proteins to intranuclear aggregates in neuronal intranuclear hyaline inclusion disease

J Neuropathol Exp Neurol. 2001 Apr;60(4):369-76. doi: 10.1093/jnen/60.4.369.


Recruitment of polyglutamine-containing proteins into nuclear inclusions (NIs) was investigated in neuronal intranuclear hyaline inclusion disease (NIHID). Some polyglutamine-containing proteins, ataxin-2, ataxin-3, and TATA box binding protein (TBP), as well as unidentified proteins with expanded polyglutamine tracts were recruited into NIs with different frequencies. Ataxin-3 was incorporated into most of the NIs and disappeared from its normal cytoplasmic localization, whereas only a small fraction of NIs contained ataxin-2 and TBP. The consistent presence of ataxin-3 in NIs could reflect a biological feature of wild-type ataxin-3, which is translocated into the nucleus under pathological conditions and participates in the formation of aggregates. Ataxin-2 also accumulated in the nucleus, but was not necessarily incorporated into NIs, suggesting that transport of these cytoplasmic proteins into the nucleus and their recruitment into NIs are not wholly explained by an interaction with a polyglutamine stretch and must be regulated in part by other mechanisms. The prevalence of ubiquitin-immunopositive NIs was inversely correlated to neuronal loss in all cases examined. This correlation could be explained if NI formation is a protective mechanism involving the ubiquitin-proteasome pathway. This hypothesis is supported by the finding that the polyglutamine epitope in the center of NIs was surrounded by ubiquitin.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Ataxin-3
  • Ataxins
  • Cell Nucleus / metabolism
  • Cell Nucleus / pathology
  • Cell Nucleus / ultrastructure
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Disease Progression
  • Fatal Outcome
  • Female
  • Glutamine / genetics
  • Glutamine / metabolism
  • Humans
  • Hyalin / metabolism*
  • Hyalin / ultrastructure
  • Immunohistochemistry
  • Inclusion Bodies / metabolism
  • Inclusion Bodies / pathology*
  • Inclusion Bodies / ultrastructure
  • Macromolecular Substances
  • Male
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurodegenerative Diseases / diagnosis
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology*
  • Neurons / metabolism
  • Neurons / pathology*
  • Neurons / ultrastructure
  • Nuclear Proteins
  • Proteins / genetics
  • Proteins / metabolism*
  • Repressor Proteins
  • TATA-Box Binding Protein
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Trinucleotide Repeats / genetics
  • Ubiquitins / metabolism


  • Ataxins
  • DNA-Binding Proteins
  • Macromolecular Substances
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Proteins
  • Repressor Proteins
  • TATA-Box Binding Protein
  • Transcription Factors
  • Ubiquitins
  • Glutamine
  • ATXN3 protein, human
  • Ataxin-3