• aggregation;
  • Alzheimer's disease;
  • secretases


We reported recently that angiotensin-converting enzyme (ACE) significantly degraded amyloid β-peptide (Aβ) to inhibit aggregation and cytotoxicity of Aβ in PC12h cells in vitro. On the other hand, others reported that ACE had two domains with highly homologous active centres, the N-domain and C-domain, but that they differed in their characteristics such as optimum chloride ion concentration, inhibition kinetics for various ACE inhibitors and rate of hydrolysis for many substrates. The aim of this study was to determine the specific ACE domain primarily responsible for degradation of Aβ. For this purpose, a series of ACE recombinant proteins, each containing only one intact domain, was constructed and expressed in COS7. Our results showed that all ACE recombinant proteins obtained were enzymatically active in terms of angiotensin I cleavage. However, inhibition of Aβ aggregation and cytotoxicity of the N-domain were higher than those of the C-domain. Reverse-phase high-performance liquid chromatography analyses confirmed that the N domain degraded Aβ. Our results indicate that the N domain of ACE is primarily responsible for the degradation of Aβ.