Amyloid Forming Proteases: Therapeutic Targets for Alzheimer's Disease

Alzheimer's disease is an age-related neurodegenerative disease which causes global loss of cognitive function. Drug treatment for Alzheimer's disease has been limited to agents that ameliorate behavioral symptoms but these agents are without effect on disease progression. Rational drug design for the treatment of Alzheimer's disease now seems possible. As a result of major advances in medical research in this area, knowledge of the etiology of Alzheimer's disease is rapidly being understood. This information has uncovered relevant and novel targets for treatment. At the center of the etiological progression of this disease is β-amyloid. A substantial body of evidence strongly suggests that this small protein is critical to the development of Alzheimer's disease. The β-amyloid protein is generated by two different proteolytic cleavages. Recently, the proteases responsible for producing the β-amyloid protein have been identified. The proteases represent viable targets for therapeutic intervention against Alzheimer's disease. In this review, we describe the biological characteristics of the β-amyloid-forming proteases in the context of pharmaceutical development.