The role and therapeutic targeting of α- ,β- and γ-secretase in Alzheimer's disease

This work is licensed under a Creative Commons Attribution 4.0 LicenseAlzheimer's disease (AD) is the most common form of dementia in the elderly and its prevalence is set to increase rapidly in coming decades. However, there are as yet no available drugs that can halt or even stabilize disease progression. One of the main pathological features of AD is the presence in the brain of senile plaques mainly composed of aggregated beta amyloid (A beta), a derivative of the longer amyloid precursor protein (APP). The amyloid hypothesis proposes that the accumulation of A beta within neural tissue is the initial event that triggers the disease. Here we review research efforts that have attempted to inhibit the generation of the A beta peptide through modulation of the activity of the proteolytic secretases that act on APP and discuss whether this is a viable therapeutic strategy for treating AD. Alzheimer's disease (AD) is the most common form of dementia in the elderly but as yet there are no drugs that can halt the progression of this disease. In a theory called the 'amyloid hypothesis', researchers have proposed that the accumulation of a small protein fragment called beta amyloid or A beta within brain tissue is the event which triggers Alzheimer's disease. A beta is a derivative of the longer amyloid precursor protein (APP). Here we review research efforts that have attempted to inhibit the generation of A beta through modulation of proteins called secretases which cut APP into A beta.