The eicosanoid pathway and brain aging

The mammalian eicosanoid pathway encompasses two major enzyme families: the lipoxygenases (LOX) that lead to synthesis of leukotrienes, and the cyclooxygenases (COX) that lead to synthesis of prostaglandins and thromboxanes. Although insects apparently also possess a functional eicosanoid pathway insect, eicosanoids have for the most part been poorly characterized. The expression in the brain of several LOX genes as well as that of COX has generally been demonstrated using methods for specific mRNA detection. Moreover, biochemical studies have demonstrated that various leukotrienes and prostaglandins can be produced in the mammalian brain, as well as in neurons. Very recently, it was proposed that in sensory neurons, the product of 12-LOX activity, 2-hydroperoxyeicosatetraenoic acid (HPETE), may act as an endogenous regulator of pain-related neuronal vanilloid (capsaicin) receptors. This chapter focuses on evidence for the neuronal presence of these enzymes and on two members of the eicosanoid pathway, 5-LOX and COX-2. However, it has to be stressed that the expression of LOX and COX enzymes in non-neuronal cells may also be important for central nervous system (CNS) functioning, particularly in certain pathologies.