• P G Mastroberardino and M Piacentini.
• Department of Genetics, Erasmus MC, Rotterdam, The Netherlands.
• J. Intern. Med. 2010 Nov 1; 268 (5): 419-31.

AbstractHuntington'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.© 2010 The Association for the Publication of the Journal of Internal Medicine.

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