Two-way cleavage of beta-amyloid protein precursor by multicatalytic proteinase. 
The beta-amyloid protein (beta-AP) derived from a beta-amyloid protein precursor (APP) is a hallmark of Alzheimer's disease.  The abundant generation of beta-AP suggests the abnormal processing of APP, but the molecular mechanism remains unclear.  The main APP-processing enzyme was purified from the rat brain and identified to be a macropain-like multicatalytic proteinase.  The purified enzyme cleaved the Gln15-Lys16 bond of beta-AP, but altered to cleave at the N-terminus of beta-AP to release the extracellular domain of beta-AP in the presence of Ca2+.  These findings suggest that the functional change in this multicatalytic proteinase may result in abnormal processing of APP.