Chapter 12 - 5-Lipoxygenase-Activating Protein Inhibitors: Promising Drugs for Treating Acute and Chronic Neuroinflammation Following Brain Injury

Abstract

As part of the innate immune response, leukotrienes initiate the first line of defense against tissue damage. They also play key pathological roles in chronic inflammatory diseases like asthma. The synthesis of leukotrienes requires two key enzymes: 5-lipoxygenase (5-LO) and 5-lipoxygenase-activating protein (FLAP). Antileukotriene therapies have been used for over 2 decades to manage asthma and include 5-LO inhibitors and the leukotriene receptor antagonists. FLAP inhibitors have also been proven safe and efficacious in asthma clinical trials but have not been brought to the market. Accumulating evidence indicates that leukotrienes mediate the pathophysiology of acute brain injuries and chronic neurodegenerative diseases. These findings have generated a renewed interest in FLAP inhibitors as interventional therapies for these disorders. In this chapter, we provide a short introduction to leukotrienes and discuss the potential use of FLAP inhibitors for treating the acute and chronic sequelae of traumatic brain injury.