Potential novel targets for Alzheimer pharmacotherapy: I. Secretases.

The prevailing major theory of Alzheimer's disease (AD) is that insoluble amyloid beta-peptide (Abeta) found in the cerebral plaques characteristic of the disease is causative or is at least a contributing factor. According to this theory, inhibition of aberrant Abeta production should prevent or at least limit the extent of AD pathophysiology. As three 'secretase' enzymes (alpha, beta and gamma) catalyse the proteolytic cleavage of amyloid precursor protein (APP) (the precursor protein of Abeta), one or more secretases have become targets for potential novel AD pharmacotherapy.