Pyro-Glu modified beta-Amyloid forms show higher toxicity
Sequential proteolytic cleavage of the Amyloid Precursor Protein (APP) by secretases (α, b, g) generates beta-Amyloid peptide fragments. Beta-Amyloid 1-42 forms is the major component of amyloid plaques in neurons of Alzheimer’s disease (AD) brains, has high aggregation/fibrillation properties and is neurotoxic.
N-terminally truncated beta-Amyloid 3-42 ad 11-42, both having a Glu as first residue, are subjected to pyro-glutamination. Pyroglutamate-modified (Pyr) beta-Amyloid 3-42 and 11-42 have been described as major compounds in the senile AD plaques. Pyro-Glu modified beta-Amyloid forms are more resistant to degradation, show higher toxicity and have increased aggregation propensity compared to the non-modified beta-Amyloid equivalent.