Transglutaminase inhibition as a possible therapeutical approach to protect cells from death in neurodegenerative diseases.

Transglutaminase inhibition as a possible therapeutical approach to protect cells from death in neurodegenerative diseases. Recent Pat CNS Drug Discov. 2013 Aug;8(2):161-8 Authors: Iannaccone M, Serretiello E, De Vivo G, Martin A, Stefanile A, Titta F, Gentile V 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. Recently, "tissue" transglutaminase (transglutaminase 2), a member of the transglutaminase family of enzymes, has been shown to be involved in the molecular mechanisms responsible for some human pathologies, including celiac disease, a very widespread human pathology. Transglutaminase activity has also been hypothesized to be involved in the pathogenetic mechanisms responsible for other several human diseases, including neurodegenerative diseases, often associated to celiac disease. Neurodegenerative diseases, such as Alzheimer's Disease, Parkinson's Disease, supranuclear palsy, Huntington's...
Source: Recent Patents on CNS Drug Discovery - Category: Drugs & Pharmacology Tags: Recent Pat CNS Drug Discov Source Type: research