Evidence for a role for transglutaminase in Huntington's disease and the potential therapeutic implications.
Transglutaminase (TGase) activity is increased in affected regions of brains from patients with Huntington's disease (HD). TGase activity is particularly elevated in the nucleus compared with the cytoplasm from these brains. Gamma-glutaminyl-lysyl cross-links have been detected in nuclear inclusions in HD brain, indicating that TGase may play a prominent role in the aggregation of huntingtin (htt). Attempts to ameliorate experimental disease, via inhibition of TGase in transgenic models of HD in mice, are under investigation.
Karpuj
Marcela V
MV
Department of Neurological Sciences, Beckman Center for Molecular Medicine, B002, Stanford University, Stanford, CA 94305, USA.
Becher
Mark W
MW
Steinman
Lawrence
L
D000818:Animals; D001921:Brain / Q000201:enzymology / Q000473:pathology; D002467:Cell Nucleus / Q000648:ultrastructure; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D002479:Inclusion Bodies / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics; D009474:Neurons / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D011503:Transglutaminases / Q000502:physiology*
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010446:Peptide Fragments; D011503:Transglutaminases