Transglutaminase activity, protein, and mRNA expression are increased in progressive supranuclear palsy.
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.
Zemaitaitis
Magdalena O
MO
Department of Pharmacology, Loyola University Stritch School of Medicine, Maywood, Illinois 60153, USA.
Kim
Soo-Youl
SY
Halverson
Robyn A
RA
Troncoso
Juan C
JC
Lee
John M
JM
Muma
Nancy A
NA
D000368:Aged; D001921:Brain / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D002529:Cerebellar Nuclei / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D015870:Gene Expression / Q000502:physiology; D005917:Globus Pallidus / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D016874:Neurofibrillary Tangles / Q000201:enzymology* / Q000473:pathology; D009474:Neurons / Q000201:enzymology* / Q000473:pathology; D011149:Pons / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013494:Supranuclear Palsy, Progressive / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
D020033:Protein Isoforms; D012333:RNA, Messenger; D016875:tau Proteins; D011503:Transglutaminases