Transglutaminase-catalyzed reactions responsible for the pathogenesis of celiac disease and neurodegenerative diseases: from basic biochemistry to clinic.

Abstract:

:Transglutaminases (TGases) are enzymes which catalyze the cross linking of a glutaminyl residue of a protein/peptide substrate to a lysyl residue of a protein/peptide co-substrate with the formation of an N-gamma-(epsilon-L-glutamyl)-L-lysine [GGEL] cross link (isopeptidic bond) and the concomitant release of ammonia. Such cross-linked proteins are often highly insoluble. The TGases are closely related enzymes and can also catalyze other important reactions for cell life. Recently, several findings concerning the relationships between the biochemical activities of the TGases and the basic molecular mechanisms responsible for some human diseases, have been reported. For example, some neurodegenerative diseases, such as Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), supranuclear palsy, etc., are characterized in part by aberrant cerebral TGase activity and by increased cross-linked proteins in affected brains. Our article describes the biochemistry and the physio-pathological roles of the TGase enzymes, with particular reference to human pathologies in which the molecular mechanism of disease can be due to biochemical activities of the tissue TGase enzyme (tTGase, type 2), such as in a very common human disease, Celiac Disease (CD), and also in certain neuropsychiatric disorders.

journal_name

Curr Med Chem

authors

Martin A,Romito G,Pepe I,De Vivo G,Merola MR,Limatola A,Gentile V

doi

10.2174/092986706777585068

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

1895-902

issue

16

eissn

0929-8673

issn

1875-533X

journal_volume

13

pub_type

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