Two‐way cleavage of β‐amyloid protein precursor by multicatalytic proteinase

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Abstract
The β‐amyloid protein (β‐AP) derived from a β‐amyloid protein precursor (APP) is a hallmark of Alzheimer's disease. The abundant generation of β‐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 β‐AP, but altered to cleave at the N‐terminus of β‐AP to release the extracellular domain of β‐AP in the presence of Ca2+. These findings suggest that the functional change in this multicatalytic proteinase may result in abnormal processing of APP.