PML nuclear bodies and neuronal intranuclear inclusion in polyglutamine diseases

Neurobiol Dis. 2003 Aug;13(3):230-7. doi: 10.1016/s0969-9961(03)00080-9.


In polyglutamine diseases, accumulation in the nucleus of mutant proteins induces the formation of neuronal intranuclear inclusions (NIIs). The nucleus is compartmentalized into structural and functional domains, which are involved in NII formation. Promyelocytic leukemia protein (PML), a major component of nuclear bodies, and mSin3A, a component of the transcription co-repressor complex, were used to investigate how the intranuclear domains/sites relate to NII formation in SCA2, SCA3, SCA7, SCA17 and DRPLA brains. We demonstrate that the size of PML-positive intranuclear structures was larger in pathological brains than in control ones and that these structures contained mutant proteins. PML colocalized only with small NIIs, which maintained the ring-like structure of normal nuclear bodies. Enlarged ring-like PML-positive structures, devoid of mutant proteins, were also found and might represent structures where mutant polyglutamine proteins have been successfully processed. These data suggest that NIIs originate from nuclear bodies, where mutant proteins accumulate for degradation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Aged
  • Cell Nucleus / pathology*
  • Central Nervous System Diseases / metabolism
  • Central Nervous System Diseases / pathology*
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Immunohistochemistry
  • Inclusion Bodies / metabolism*
  • Inclusion Bodies / pathology
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Proteins / metabolism*
  • Neurons / metabolism
  • Neurons / pathology*
  • Nuclear Proteins*
  • Peptides / genetics
  • Peptides / metabolism*
  • Promyelocytic Leukemia Protein
  • Transcription Factors / metabolism*
  • Tumor Suppressor Proteins


  • Neoplasm Proteins
  • Nuclear Proteins
  • Peptides
  • Promyelocytic Leukemia Protein
  • Transcription Factors
  • Tumor Suppressor Proteins
  • PML protein, human
  • polyglutamine