The potential application of cyclo-oxygenase type 2 inhibitors to Alzheimer's disease

In recent years, dramatic progress has been made in the understanding of the neurogenetics and neurobiology of Alzheimer's disease (AD). A great deal of experimental evidence has accumulated to support the hypothesis that inflammatory mechanisms are involved in the pathophysiology of AD. In addition, epidemiological studies have revealed that anti-inflammatory medications reduce the risk of developing AD. However, long-term use of conventional anti-inflammatory drugs is associated with significant toxicity which limits their potential application to the treatment or prevention of AD. It is believed that the inhibition of cyclo-oxygenase type-1 (COX-1) causes much of this toxicity, while inhibition of COX type-2 (COX-2), which is induced by inflammatory stimuli, may confer the anti-inflammatory effect. COX-2 is also constitutively expressed in brain regions preferentially affected in Alzheimer's disease and may be directly involved in neuronal cell death. Therefore, selective COX-2 inhibitors represent a promising class of drugs for the treatment of AD.