Abstract
Orexins [orexin-A (OXA) and orexin-B (OXB)] are two isoforms of neuropeptides produced by the hypothalamus. The main biological actions of orexins, focused on the central nervous system, are to control the sleep/wake process, appetite and feeding, energy homeostasis, drug addiction, and cognitive processes. These effects are mediated by two G protein-coupled receptor (GPCR) subtypes named OX1R and OX2R. In accordance with the synergic and dynamic relationship between the nervous and immune systems, orexins also have neuroprotective and immuno-regulatory (i.e., anti-inflammatory) properties. The present review gathers recent data demonstrating that orexins may have a therapeutic potential in several pathologies with an immune component including multiple sclerosis, Alzheimer's disease, narcolepsy, obesity, intestinal bowel diseases, septic shock, and cancers.
Highlights
The G protein-coupled receptors (GPCR) constitute the largest family of membrane receptors with more than 800 sequences encoded by about 4% of the human genome [1]
Despite the scarcity of data regarding the expression of orexin receptors in immune cells, we found that OX1R and OX2R receptors are expressed in murine central and peripheral immune cell tissues, and in sorted T (CD4+ and CD8+) and myeloid (CD11b+) cells [79]
Duncan et al tested whether a chronic administration of a dual orexin receptor antagonist (DORA) would favor sleep enhancement and attenuate the development of Alzheimer’s disease (AD) by reducing neuropathology, neuroinflammation, and cognitive deficits
Summary
The main biological actions of orexins, focused on the central nervous system, are to control the sleep/wake process, appetite and feeding, energy homeostasis, drug addiction, and cognitive processes. These effects are mediated by two G protein-coupled receptor (GPCR) subtypes named OX1R and OX2R. In accordance with the synergic and dynamic relationship between the nervous and immune systems, orexins have neuroprotective and immuno-regulatory (i.e., anti-inflammatory) properties. The present review gathers recent data demonstrating that orexins may have a therapeutic potential in several pathologies with an immune component including multiple sclerosis, Alzheimer’s disease, narcolepsy, obesity, intestinal bowel diseases, septic shock, and cancers
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