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Minerva Biotecnologica 2002 June;14(2):171-6

Copyright © 2003 EDIZIONI MINERVA MEDICA

language: English

Tissue transglutaminase in neurodegenerative diseases

Johnson G. V. W., Bailey C. D., Tucholski J., Lesort M.

Department of Psychiatry, University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA


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Tis­sue trans­glu­tam­i­nase (tTG), a mul­ti­func­tion­al pro­tein, is the ­most abun­dant trans­glu­tam­i­nase in ­human ­brain, and like­ly to ­play a ­role in reg­u­lat­ing neu­ro­nal func­tion. Tis­sue TG post-­tran­sla­tion­al­ly mod­i­fies pro­teins by trans­am­i­da­tion of spe­cif­ic glu­ta­mine res­i­dues. ­This ­action ­results in the incor­po­ra­tion of poly­amines ­into sub­strate pro­teins or the for­ma­tion of pro­tein cross­links, mod­ifi­ca­tions ­that like­ly ­have sig­nif­i­cant ­effects on neu­ro­nal func­tion. Tis­sue TG is a ­unique mem­ber of the trans­glu­tam­i­nase fam­i­ly as in addi­tion to cat­a­lyz­ing the cal­cium-depen­dent trans­am­i­da­tion reac­tion, it ­also ­binds and hydro­lyz­es GTP and may ­play a ­role in sig­nal trans­duc­tion. Fur­ther, bind­ing of gua­nine nucle­o­tides inhib­its the trans­am­i­dat­ing activ­ity of tTG. Sev­er­al ­roles for tTG in neu­ro­nal func­tion ­have ­been pos­tu­lat­ed, and ­there is evi­dence ­that tTG may ­also ­play a ­role in apop­to­sis. ­Recent find­ings ­have pro­vid­ed evi­dence ­that dys­reg­u­la­tion of tTG may con­trib­ute to the path­o­gen­e­sis of ­Alzheimer’s dis­ease and ­Huntington’s dis­ease, and per­haps oth­er neu­ro­de­gen­er­a­tive con­di­tions. In ­both ­Alzheimer’s and ­Huntington’s dis­ease tTG and TG activ­ity are ele­vat­ed com­pared to age-­matched con­trols. Fur­ther, immu­no­his­to­chem­i­cal stud­ies ­have dem­on­strat­ed ­that ­there is an ­increase in tTG reac­tiv­ity in affect­ed neu­rons in ­both ­Alzheimer’s and ­Hunting-ton’s dis­ease ­brain. ­Although intri­guing, ­many ques­tions ­remain to be ­addressed to defin­i­tive­ly estab­lish a ­role for tTG in ­these neu­ro­de­gen­er­a­tive dis­eas­es.

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