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Keywords:

  • epigenetics;
  • Huntington's disease;
  • PGC-1-alpha;
  • transcription;
  • transglutaminase

Abstract

The article by McConoughey et al in the current issue of EMBO Molecular Medicine examines the contribution of transglutaminase 2 (TG2) to Huntington's disease (HD) pathogenesis. The authors find that TG2 inhibition can ameliorate HD neurodegeneration, and thereby elevate the status of transglutaminases (TGs) to a major therapeutic target—not because of their well-known activity in mutant protein aggregation, but instead based upon their ability to epigenetically modulate transcription and energy production. While the reintroduction of TG inhibition as a therapy for HD may evoke feelings of déjà vu, the outcome this time around could go in a dramatically different direction.

See related article in EMBO Mol Med (Stephen J. McConoughey et al. (2010) EMBO Mol Med 2: 349–370)