Effect of inflammatory mediators and their inhibitors on Dementia

Abstract

Dementia is a decline of cognitive functions (reasoning, memory, and other mental disorders). It is caused by a damage in the brain tissue, causing disturbed brain functioning. Studies on Alzheimer’s have led to major revaluation of concept such as ‘Neuroinflammation’. Proinflammatory mediators released by activated glial cells during brain inflammation have been proposed to contribute to neuropatholology underlying cognitive deficits. Glial- derived proinflammatory cytokines such as IL-1β, IL-6, TNF-α, TGF-β set a spectrum of signalling events which influence in neurological disease and disorder. These proinflammatory cytokines induce nitric oxide synthase and COX-2 activity in astrocytes, leading to release of free radicals and oxidative stress causing neuronal death. NSAIDS have been reported to reduce the risk for AD, by decreasing neuroinflammation. Further double-blind clinical trial of COX-1 inhibitor showed arrest in the progression of disease, but due to serious side effects of NSAIDS their use in geriatric population is limited. As there are various inflammatory mediators involved in inflammation, they can be used as a new therapeutic approach in AD, such as TNF-α inhibitors, IL-1 inhibitors, new COX or Prostaglandins modulators. In this review we will discuss about the role of inflammatory mediators in Pathophysiology of neuroinflammation leading to dementia and role of their inhibitors in treatment of dementia.