Aluminum inhibits proteolytic degradation of amyloid β peptide by cathepsin D: A potential link between aluminum accumulation and neuritic plaque deposition

Neuritic plaques are the key pathological feature of Alzheimer’s disease, and amyloid β (Aβ) peptides are major component of these plaques. In this study, we demonstrated the influence of aluminum (Al) on the Aβ peptide degradation by cathepsin D. Al did not directly affect the cathepsin D activity using small synthetic substrate. However, when Aβ peptides were used as substrate, the apparent inhibitory effect of Al on cathepsin D activity was observed. This inhibitory effect disappeared by treatment of desferrioxamine. These results indicate that Al has the potential to interact and disrupt Aβ peptide catabolism via the inhibition of proteolytic degradation.