Possible involvement of transglutaminase-catalyzed reactions in the physiopathology of neurodegenerative diseases

  title={Possible involvement of transglutaminase-catalyzed reactions in the physiopathology of neurodegenerative diseases},
  author={Antonio Mart{\'i}n and Alessandro Giuliano and Domenico Collaro and Giulia De Vivo and Carla Sedia and Enrica Serretiello and Vittorio Gentile},
  journal={Amino Acids},
Transglutaminases are ubiquitous enzymes, which catalyze post-translational modifications of proteins. Recently, transglutaminases and tranglutaminase-catalyzed post-translational modification of proteins have been shown to be involved in the molecular mechanisms responsible for several human diseases. Transglutaminase activity has been hypothesized to be involved also in the pathogenetic mechanisms responsible for human neurodegenerative diseases. Neurodegenerative diseases, such as Alzheimer… Expand
Computational investigation of small-molecule human tissue transglutaminase inhibitors
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Isopeptidase activity of human transglutaminase 2: disconnection from transamidation and characterization by kinetic parameters
The W278F mutation resulted in six times elevated amine incorporating transamidase activity demonstrating the regulatory significance of W278 and W332 in TG2 and that mutations can change opposed activities located at the same active site. Expand
Applications for Treatment of Neurodegenerative Diseases
Hallmark of neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and prion diseases is aggregation of various proteins, which accumulate in the brain. The early stages of aggregation areExpand
Calcium‐dependent activation of transglutaminase 2 by nanosecond pulsed electric fields
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Thymosin β4 and Tissue Transglutaminase. Molecular Characterization of Cyclic Thymosin β4
In spite of 3 glutaminyl and 9 lysyl residues of thymosin β4 only one isopeptide bond between Lys16 and Gln36 was formed and these two amino acid residues are conserved in all β-thymosins. Expand
Biomedical Applications of Acridines
Acridines interact with both nucleic acids and proteins. The targeting of these biopolymers is broadly applied in cancer therapy and gene delivery. Interestingly, due to direct interactions ofExpand
Transglutaminases: future perspectives
PrefaceThis is the third special issue focused on “Transglutaminases” that is now available on this journal and dedicated to one of the pioneers of these enzymes, John Edward Folk, who died DecemberExpand
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Pathogenic Angiogenic Mechanisms in Alzheimer's Disease
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Differential Expression of Multiple Transglutaminases in Human Brain
It is demonstrated by reverse transcriptase-polymerase chain reaction and immunological methods with specific antibodies that in fact three members of the transglutaminase family of enzymes are involved in normal neuronal structure and function, but their elevated expression and cross-linking activity may also contribute to neuronal degenerative disease. Expand
Protein crosslinking, tissue transglutaminase, alternative splicing and neurodegeneration
Elevated expression and alternative splicing, resulting in a short (S) isoform of tTG with more active crosslinking activity, are associated with increased neuronal loss in affected regions in the demented brain. Expand
Inhibition of transglutaminase 2 mitigates transcriptional dysregulation in models of Huntington disease
It is demonstrated that selective TG inhibition broadly corrects transcriptional dysregulation in HD and defines a novel HDAC‐independent epigenetic strategy for treating neurodegeneration. Expand
Transglutaminases and Transglutaminase‐Catalyzed Cross‐Links Colocalize with the Pathological Lesions in Alzheimer's Disease Brain
It is concluded that these TGs demonstrate cross‐linking activity in AD lesions, which suggests that both TG1 and TG2 are likely involved in the protein aggregation processes underlying the formation of SPs, CAA and/or NFTs in AD brain. Expand
Transglutaminase Activity, Protein, and mRNA Expression Are Increased in Progressive Supranuclear Palsy
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 and may be potential targets for therapeutic intervention. Expand
Transglutaminase cross-linking of the tau protein.
These experiments demonstrate that the enzyme modifies tau at only one or a few discrete sites, primarily in the carboxyl half of the molecule, and provides evidence that the cross-linking reaction is specific, and requires that the substrates be appropriately associated for cross- linking to occur. Expand
Therapeutic Effects of Cystamine in a Murine Model of Huntington's Disease
Treatment in R6/2 transgenic HD mice, using the transglutaminase inhibitor cystamine, significantly extended survival, improved body weight and motor performance, and delayed the neuropathological sequela. Expand
Cystamine Inhibits Caspase Activity
It is demonstrated that cystamine may prolong neuronal survival and delay the onset of HD by inhibiting caspases and increasing the level of antioxidants such as glutathione. Expand
Localization of transglutaminase in hippocampal neurons: implications for Alzheimer's disease.
The results suggest that TGase may be associated with the neurofibrillary degeneration observed in AD, thereby implicating TGase as a potential factor in the pathogenesis of Alzheimer's disease. Expand
Intron-Exon Swapping of Transglutaminase mRNA and Neuronal Tau Aggregation in Alzheimer's Disease*
The current results identify intron-exon “switching” between L and S isoforms, implicating G-protein-coupled signaling pathways associated with tTG that may help to determine the dual roles of this enzyme in neuronal life and death processes. Expand