Robyn Tamboli
Last active: 1/23/2018

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

Zemaitaitis MO, Kim SY, Halverson RA, Troncoso JC, Lee JM, Muma NA
J Neuropathol Exp Neurol. 2003 62 (2): 173-84

PMID: 12578227 · DOI:10.1093/jnen/62.2.173

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.

MeSH Terms (14)

Aged Brain Cerebellar Nuclei Gene Expression Globus Pallidus Humans Neurofibrillary Tangles Neurons Pons Protein Isoforms RNA, Messenger Supranuclear Palsy, Progressive tau Proteins Transglutaminases

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