Therapeutic Potential of ?-Secretase in Alzheimer's Disease / 生物化学与生物物理进展

ABSTRACT

Alzheimer!s disease (AD) is one of the commonest neurodegenerative diseases affected mainly theelderly. AD is characterized by the formation of neuritic plaque in brain, which is composed mainly of extracellular?amyloid deposion, the A?. A?is deprived from serial hydrolysis of amyloid precursor protein (APP) by twosecretases, the ?and ?-secretase respectively. Alternatively, APP can also be sequential processed by ?-secretaseand ?-secretase, which not only preclude the formation of A?, but also generate a large ectodomain (sAPP?) whohas several neuroprotective properties. Thus the secondary processing pathway has become the focus of ADresearch. 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 ?-secretase. Here the biological characteristics of?-secretase, its activity regulation and its potential function as targets for the treatment of AD were summerized.