γ-Glutamylamines and neurodegenerative diseases

Transglutaminases catalyze the formation of gamma-glutamylamines utilizing glutamyl residues and amine-bearing compounds such as lysyl residues and polyamines. These gamma-glutamylamines can be released from proteins by proteases in an intact form. The free gamma-glutamylamines can be catabolized to 5-oxo-L-proline and the free amine by gamma-glutamylamine cyclotransferase. Free gamma-glutamylamines, however, accumulate in the CSF and affected areas of Huntington Disease brain. This observation suggests transglutaminase-derived gamma-glutamylamines may play a more significant role in neurodegeneration than previously thought. The following monograph reviews the metabolism of gamma-glutamylamines and examines the possibility that these species contribute to neurodegeneration.