In search of an enzyme: the β-secretase of Alzheimer's disease is an aspartic proteinase

Abstract The deposition of beta-amyloid (Aβ) in the brain is a neuropathological feature of Alzheimer's disease. Aβ is cleaved from its precursor protein (APP) by processing at its N and C termini by enzymes known as β- and γ-secretases,respectively. The identity of these enzymes has been elusive but the search for the N-terminal secretase might have ended recently with the almost simultaneous publication by five major laboratories claiming a transmembrane aspartic proteinase to be the long sought after β-secretase. Even at this early stage of its characterization, this aspartic proteinase fulfils many of the key criteria necessary for β-secretase.The race is now on to develop inhibitors that could prove effective in halting the progression of Alzheimer's disease.