Transglutaminase activity, protein, and mRNA expression are increased in progressive supranuclear palsy

Magdalena O. Zemaitaitis, Soo Youl Kim, Robyn A. Halverson, Juan C. Troncoso, John M. Lee, Nancy A. Muma

Research output: Contribution to journalArticle

Abstract

Transglutaminases catalyze the covalent cross-linking of substrate proteins to form insoluble protein complexes that are resistant to degradation. Our previous studies demonstrated that transglutaminase-induced cross-linking of tau proteins occurs in Alzheimer disease and progressive supranuclear palsy (PSP). The current study was designed to measure transglutaminase enzyme activity and the mRNA and protein levels of 3 transglutaminase isoforms that are expressed in human brain. Overall, transglutaminase activity was significantly increased in the globus pallidus (182% of control) and pons in PSP (171% of control) but not the occipital cortex (a region spared from pathology). Using a Spearman rank correlation test, we found that tissues with more transglutaminase-activity had more neurofibrillary tangles. Protein and mRNA levels of transglutaminase 1 were increased in globus pallidus of PSP as compared to controls. There were also significantly higher mRNA levels of the short form of transglutaminase 2 in globus pallidus of PSP (974% of control). Transglutaminase 1 mRNA and the long isoform of transglutaminase 2 mRNA (2212% of control) were significantly higher in PSP in the dentate of cerebellum. Together, these findings suggest that transglutaminase 1 and 2 enzymes may be involved in the formation and/or stabilization of neurofibrillary tangles in selectively vulnerable brain regions in PSP. These transglutaminases may be potential targets for therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)173-184
Number of pages12
JournalJournal of neuropathology and experimental neurology
Volume62
Issue number2
DOIs
StatePublished - Feb 1 2003

Keywords

  • Cross-linking
  • Neurodegeneration
  • Progressive supranuclear palsy (PSP)
  • Tauopathy
  • Transglutaminase

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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