Therapeutic potential of α-secretase in Alzheimer's disease

Alzheimer's disease (AD) is one of the commonest neurodegenerative diseases affected mainly the elderly. AD is characterized by the formation of neuritic plaque in brain, which is composed mainly of extracellular beta amyloid deposion, the A beta. A beta is deprived from serial hydrolysis of amyloid precursor protein (APP) by two secretases, the beta and gamma-secretase respectively. Alternatively, APP can also be sequential processed by alpha-secretase and gamma-secretase, which not only preclude the formation of A beta, but also generate a large ectodomain (sAPP alpha) who has several neuroprotective properties. Thus the secondary processing pathway has become the focus of AD research. Many results have indicated that members of the adamalysin family of proteins, mainly the ADAM 10, ADAM 17 and ADAM 9, fulfill some of the criteria required of (x-secretase. Here the biological characteristics of a-secretase, its activity regulation and its potential function as targets for the treatment of AD were summerized.