Neuroprotective effects of nonsteroidal anti-inflammatory drugs on neurodegenerative diseases

It is well known that nonsteroidal anti-inflammatory drugs (NSAIDs) possess anti-inflammatory, analgesic and antipyretic properties by inhibiting cyclooxygenase (COX), a prostaglandin-synthesizing enzyme. It has also been revealed that NSAIDs exert inhibitory effects on the generating system of nitric oxide radicals and modulating effects on transcription factors which are related to inflammatory reactions including cytokine expression. Recently, a number of studies have been conducted focusing on the neuroprotective effects of NSAIDs, since it has been reported that inflammatory processes are associated with the pathogenesis of several neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. In the experimental model of Parkinson's disease, NSAIDs have also exerted neuroprotective effects which are based not only on their COX-inhibiting effects but also on other properties: inhibitory effects on nitric oxide synthesis, action as agonists for peroxisome proliferator-activated receptor gamma, and some unknown pharmacological effects. In this article, various pharmacological effects of NSAIDs except their inhibitory action on COX are reviewed, and possible neuroprotective effects of NSAIDs have been discussed on neurodegenerative diseases, especially Parkinson's disease.