Transglutaminase facilitates the formation of polymers of the beta-amyloid peptide.
One of the major pathological characteristics of Alzheimer's disease is the increased number of amyloid-containing senile plaques within the brain. The dense cores of these plaques are composed primarily of highly insoluble aggregates of a 39-43-residue peptide referred to as the beta-amyloid peptide (beta A). The mechanisms by which these insoluble extracellular deposits of beta A are formed remain unknown. In this study, the cross-linking of beta A by the calcium-dependent enzyme, transglutaminase was examined. Transglutaminases are a family of enzymes which are found in brain, and catalyse the cross-linking of specific proteins into insoluble polymers. Synthetic beta A (1-40) was readily cross-linked by transglutaminase, forming multimers in a time-dependent fashion. Furthermore, a second peptide with a substitution similar to that in the Dutch-type hereditary amyloidosis mutation (Glu22 to Gln) was also found to be a substrate for transglutaminase. Since transglutaminase covalently cross-links proteins through glutamine residues, it is suggested that transglutaminase contributes to amyloid deposition in Dutch-type hereditary amyloidosis, and possibly Alzheimer's disease.
Dudek
S M
SM
Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham 35294-0017.
Johnson
G V
GV
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000686:Amyloidosis / Q000235:genetics / Q000378:metabolism; D005998:Glycine / Q000235:genetics; D006801:Humans; D008239:Lysine / Q000235:genetics; D009154:Mutation; D011503:Transglutaminases / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D011503:Transglutaminases; D008239:Lysine; D005998:Glycine