| Popis: |
β-secretase has been identified as a novel membrane-tethered member of the aspartyl proteases, termed β-site APP cleaving enzyme 1 (BACE1). The generation of BACE1 null mice has clearly demonstrated that BACE1 is the limiting enzyme for Aβ generation. Initial studies showed that genetic deletion of BACE1 did not produce any overt phenotype, suggesting that inhibiting BACE1 pharmacologically would be a straightforward strategy for Alzheimer’s disease (AD) treatment. However, following studies identified a multitude of phenotypes in BACE1 null mice. While these findings shed some light on BACE1 function, they also raise concerns about the possible side effects of therapeutic BACE1 inhibition. On the other hand, increasing evidence suggests that BACE1 is a stress-induced protease that is increased in AD brains and following experimental traumatic brain injury. Thus, the search for therapeutic targets aimed to restore normal levels of BACE1 represents an attractive alternative approach to the direct inhibition of BACE1. |
