title: Transglutaminase activity as a possible therapeutical target in neurodegenerative diseases.
abstract: Transglutaminases are ubiquitous enzymes which catalyze post-translational modifications of proteins. The main activity of these enzymes is the cross-linking of glutaminyl residues of a protein/peptide substrate to lysyl residues of a protein/peptide co-substrate. In addition to lysyl residues, other second nucleophilic co-substrates may include monoamines or polyamines (to form mono- or bi-substituted /crosslinked adducts) or -OH groups (to form ester linkages). In absence of co-substrates, the nucleophile may be water, resulting in the net deamidation of the glutaminyl residue. Transglutaminase activity has been suggested to be involved in molecular mechanisms responsible for both physiological or pathological processes. For example, neurodegenerative diseases, such as Alzheimer's Disease, Parkinson's Disease, supranuclear palsy, Huntington's Disease and other polyglutamine diseases, are characterized in part by aberrant cerebral transglutaminase activity and by increased cross-linked proteins in affected brains. This review focuses on the possible molecular mechanisms responsible for such diseases and on the possible therapeutic effects of selective transglutaminase inhibitors for patients with diseases characterized by aberrant transglutaminase activity. The article presents some promising patents on the transglutaminase activity.
authors.forename: Martina
authors.initials: M
authors.lastname: Iannaccone
authors.forename: Federica
authors.initials: F
authors.lastname: Titta
authors.forename: Enrica
authors.initials: E
authors.lastname: Serretiello
authors.forename: Giulia
authors.initials: G
authors.lastname: De Vivo
authors.forename: Antonio
authors.initials: A
authors.lastname: Martin
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, via Costantinopoli 16, 80138 Naples, Italy. vittorio.gentile@unina2.it.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Gentile
mesh_terms: D001921:Brain / Q000201:enzymology*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000201:enzymology; D010330:Patents as Topic; D011503:Transglutaminases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D011503:Transglutaminases