Type 2 transglutaminase in Huntington’s disease: a double‐edged sword with clinical potential

.  Mastroberardino PG, Piacentini M (Erasmus MC, Rotterdam, The Netherlands; University of Pittsburgh, Pittsburgh, PA, USA; University of Rome ‘Tor Vergata’, and National Institute for Infectious Diseases IRCCS ‘Lazzaro Spallanzani’, Rome, Italy) Type 2 transglutaminase in Huntington’s disease: a do...

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Published in:Journal of internal medicine 2010-11, Vol.268 (5), p.419-431
Main Authors: Mastroberardino, P. G., Piacentini, M.
Format: Article
Language:English
Subjects:
Adult and adolescent clinical studies
Animals
autophagy
Autophagy - physiology
Biological and medical sciences
Cell Death - physiology
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
General aspects
GTP-Binding Proteins - antagonists & inhibitors
GTP-Binding Proteins - physiology
Humans
Huntington Disease - drug therapy
Huntington Disease - enzymology
Huntington’s disease
intracellular inclusions
Medical sciences
Mice
Mitochondria - enzymology
Mitochondria - physiology
Models, Animal
Neurology
Organic mental disorders. Neuropsychology
Protein Glutamine gamma Glutamyltransferase 2
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
therapeuthics
transglutaminase 2
Transglutaminases - antagonists & inhibitors
Transglutaminases - physiology
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Summary:.  Mastroberardino PG, Piacentini M (Erasmus MC, Rotterdam, The Netherlands; University of Pittsburgh, Pittsburgh, PA, USA; University of Rome ‘Tor Vergata’, and National Institute for Infectious Diseases IRCCS ‘Lazzaro Spallanzani’, Rome, Italy) Type 2 transglutaminase in Huntington’s disease: a double‐edged sword with clinical potential (Review‐Symposium). J Intern Med 2010; 268: 419–431. Huntington’s disease (HD) is a dominant genetic neurodegenerative disorder. The pathology affects principally neurons in the basal ganglia circuits and terminates invariably in death. There is compelling necessity for safe and effective therapeutic strategies to arrest, or even retard the progression of the pathogenesis. Recent findings indicate the autophagy‐lysosome systems as appealing targets for pharmacological intervention. Autophagy exerts a critical role in controlling neuronal protein homeostasis, which is perturbed in HD, and is compromised in the pathogenesis of several neurodegenerative diseases. Type 2 transglutaminase (TG2) plays an important role both in apoptosis and autophagy regulation, and accumulates at high levels in cells under stressful conditions. TG2 inhibition, achieved either via drug treatments or genetic approaches, has been shown to be beneficial for the treatment of HD in animal models. In this review we will discuss the relevance of TG2 to the pathogenesis of HD, in an effort to define novel therapeutic avenues.
ISSN:0954-6820
1365-2796
DOI:10.1111/j.1365-2796.2010.02275.x