Simultaneous binding of heme and Cu with amyloid β peptides: active site and reactivities

Amyloid imbalance and A beta plaque formation are key histopathological features of Alzheimer's disease (AD). These amyloid plaques observed in post-mortem AD brains have been found to contain increased levels of Cu and deposition of the heme cofactor. The increased Cu concentration and heme co-localization together with other heme related dysfunctions hint towards the likely association of the metal and cofactor in the pathology of the disease. Heme and Cu bind with A beta separately to form heme-A beta and Cu-A beta complexes, respectively. In addition, the metal and cofactor can simultaneously bind with the peptide to generate a physiologically relevant heme-Cu-A beta complex. In this review, we discuss the active site environment, electronic structure, spectroscopic and electrochemical properties, and some interesting reactivities exhibited by the heme-Cu-A beta complex with small molecules, such as oxygen (O-2), nitric oxide (NO) and nitrite (NO2-).

Automated summary

Amyloid imbalance and A beta plaque formation are key features of Alzheimer's disease. The plaques contain increased levels of Cu and deposition of the heme cofactor, suggesting a possible association of the metal and cofactor in the pathology. Heme and Cu bind with A beta separately to form heme-A beta and Cu-A beta complexes, and they can also bind simultaneously to generate a heme-Cu-A beta complex.