Abstract
The effect of soluble amyloid beta-protein (sAβ) and fibrillar amyloid beta-protein (fAβ) on the casein-digesting activity of high molecular weight bovine brain protease (HMW protease) and trypsin was studied. While sAβ stimulated the casein-digesting activity of HMW protease in a concentration-dependent manner, it did not affect trypsin activity. Structure-activity relationship was studied by testing different soluble and fibrillar Aβ peptides. Various Aβ peptides affected casein-digesting activity of HMW protease differently: sAβ 1–40 > sAβ 22–35 = sAβ 1–11 = sAβ1–16 > sAβ 1–28 = sAβ 31–35, while sAβ 12–28 and sAβ 25–35 had no effect. On the other hand, among the fibrillar Aβ peptides, only fAβ 1–40 significantly inhibited the casein-digesting activity of HMW protease. Tricine gel electrophoresis showed that sAβ was digested by trypsin while it remained un-cleaved in the presence of HMW protease. However, fAβ, a major component of amyloid plaques in Alzheimer's disease, inhibited the casein-digesting activity of both HMW protease and trypsin. fAβ was found to be resistant to proteolysis by HMW protease and trypsin. The trypsin resistance starts in the early stage of fibrillization of Aβ, i.e., aggregated Aβ. Taken together, these results suggest that fibrillization of Aβ may affect the clearance of Aβ by inhibiting the brain proteases, thereby increasing the concentration of circulating Aβ, that may further increase the Aβ fibrillization.