Abstract
Orexins, also known as hypocretins, are two neuropeptides secreted from orexin-containing neurons, mainly in the lateral hypothalamus (LH). Orexins orchestrate their effects by binding and activating two G-protein–coupled receptors (GPCRs), orexin receptor type 1 (OX1R) and type 2 (OX2R). Orexin/receptor pathways play vital regulatory roles in many physiological processes, especially feeding behavior, sleep–wake rhythm, reward and addiction and energy balance. Furthermore several reports showed that orexin/receptor pathways are involved in pathological processes of neurological diseases such as narcolepsy, depression, ischemic stroke, drug addiction and Alzheimer’s disease (AD). This review article summarizes the expression patterns, physiological functions and potential molecular mechanisms of the orexin/receptor system in neurological diseases, providing an overall framework for considering these pathways from the standpoints of basic research and clinical treatment of neurological diseases.
Highlights
The orexins, known as hypocretins, are a pair of neuropeptides that are mainly derived from orexin-containing neurons in the lateral hypothalamus (LH)
These results revealed that orexin receptors activate a novel mechanism of [Ca2+]i elevation via nonselective cation channels (NSCCs), in contrast to the original notion that the changes in calcium levels were mediated primarily through G-protein–coupled receptors (GPCRs)
OA affects rat insulinoma cell proliferation via stimulation of the AKT signaling pathway by OX1R (Chen et al, 2013). These results show that the orexin/receptor system can activate potent intracellular signaling via pathways other than the classical signaling pathways (Figure 3)
Summary
The orexins, known as hypocretins, are a pair of neuropeptides that are mainly derived from orexin-containing neurons in the lateral hypothalamus (LH). Subsequent experiments revealed many other important physiological functions of these peptides, including regulation of the sleep–wake cycle (de Lecea and Sutcliffe, 2005; Chow and Cao, 2016), energy homeostasis (Tsuneki et al, 2012), neuroendocrine functions (Inutsuka and Yamanaka, 2013), glucose metabolism (Tsuneki et al, 2016), stress-adaptive responses (Xiao et al, 2013) and reward-seeking and drug addiction (Aston-Jones et al, 2010) Orexins bind their cognate G-protein–coupled receptors (GPCRs), orexin receptor type 1 (OX1R, named as Hcrtr-1) and type 2 (OX2R, or Hcrtr-2), which activate different downstream signal pathways, thereby exerting a variety of physiological functions (Sakurai et al, 1998). These discussions summarize our current knowledge of the orexin/receptor system and the prospects for applying this information to the clinical treatment of neurological diseases
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
