ABSTRACT
The abnormal accumulation of ß-amyloid (Aß) in the brain is an early and invariant feature of Alzheimer’s disease and is believed to play a pivotal role in the etiology and pathogenesis of the disease. The concentration of Aß is regulated by multiple enzy matic activities, including proteases responsible for its degradation. In this chapter we present evidence for endothelin-converting enzymes (ECEs) as Aß-degrading enzymes. Overexpression of ЕСЕ-1 in cultured cells reduces Aß accumulation by up to 90%, and the enzyme is capable of directly cleaving Aß at multiple sites. As ECEs are expressed in brain, reduced ЕСЕ activity by genetic mutation, altered transcriptional activity, or pharmacological inhibition, for ex ample, may be a risk factor for Alzheimer’s disease (AD). The risk of pharmacological reduc tion of ЕСЕ activity is of particular concern since ЕСЕ inhibitors are being developed for the treatment of hypertension and other disorders.
