Roles of N-acylethanolamines in brain functions and neuropsychiatric diseases

N-acylethanolamines (NAEs) are bioactive lipids, structural analogues to the endocannabinoid arachidonoylethanolamide (anandamide), whose functions and properties are being elucidated in recent years. By activating their receptors, specifically peroxisome proliferator-activated receptors (PPARs), these molecules exert a variety of physiological effects via genomic and rapid non-genomic mechanisms. Regulation of lipid metabolism, energy homeostasis, and anti-inflammation are among the best-characterized effects of PPAR activation. NAEs are abundant in the CNS and their receptors are widely expressed both in neurons and in glial cells, where they modulate brain functions and are involved in the pathophysiology of neurological and psychiatric disorders. In the brain, they participate in the regulation of feeding behavior, cognitive functions, mood, reward, and sleep-wake cycles, and evidence suggests that they might be therapeutically exploited as neuroprotective agents, “anti-addictive” medications, anticonvulsant, and antidepressant. In this chapter, we will review the state of the art on these neuromodulators and their receptors in the brain and will discuss new hypotheses on their physiological and pathophysiological roles.