Neuroinflammation Targeting Pyroptosis: Molecular Mechanisms and Therapeutic Perspectives in Stroke.

Pyroptosis is a recently identified type of pro-inflammatory programmed cell death (PCD) mediated by inflammasomes and nucleotide oligomerization domain-like receptors (NLs) and dependent on members of the caspase family. Pyroptosis has been widely reported to participate in the occurrence and progression of various inflammatory diseases, including stroke, a frequently lethal disease with high prevalence and many complications. To date, there have been no effectively therapeutic strategies and methods for treating stroke.

Research progress on the role of orphan receptor GPR139 in neuropsychiatric behaviours.

The study of orphan G protein-coupled receptors (GPCRs) holds much promise for increasing our understanding of neuropsychiatric diseases and for the development of new therapeutic strategies for these diseases. GPR139 is an orphan GPCR expressed in the central nervous system, especially in areas of the brain that control movement, motivation, and reward, and those that regulate neuropsychiatric behaviour. This review provides information about the discovery, tissue expression, signal transduction pathways, and physiological functions of GPR139, as well as how GPR139 interacts with other GPCRs, which form heteromeric complexes that affect their pharmacology and function.

Apelin-13 prevents the effects of oxygen-glucose deprivation/reperfusion on bEnd.3 cells by inhibiting AKT-mTOR signaling.

Autophagy plays works by degrading misfolded proteins and dysfunctional organelles and maintains intracellular homeostasis. Apelin-13 has been investigated as an agent that might protect the blood-brain barrier (BBB) from cerebral ischemia/reperfusion (I/R) injury. In this study, we examined whether apelin-13 protects cerebral microvascular endothelial cells, important components of the BBB, from I/R injury by regulating autophagy.

Orexin-A alleviates astrocytic apoptosis and inflammation via inhibiting OX1R-mediated NF-κB and MAPK signaling pathways in cerebral ischemia/reperfusion injury.

Orexin-A (OXA) is a neuropeptide with neuroprotective effect by reducing cerebral ischemia/reperfusion injury (CIRI). Inflammation and apoptosis mediated by astrocyte activation are the key pathological mechanisms for CIRI. We thus attempted to confirm neuroprotective effects of OXA on astrocytic inflammation and apoptosis in CIRI and clarify the relative mechanisms.

The Effects of Apelin and Elabela Ligands on Apelin Receptor Distinct Signaling Profiles.

Apelin and Elabela are endogenous peptide ligands for Apelin receptor (APJ), a widely expressed G protein-coupled receptor. They constitute a spatiotemporal dual ligand system to control APJ signal transduction and function. We investigated the effects of Apelin-13, pGlu-apelin-13, Apelin-17, Apelin-36, Elabela-21 and Elabela-32 peptides on APJ signal transduction.

Orexin-A alleviates cerebral ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress-mediated apoptosis.

Orexin‑A (OXA) protects neurons against cerebral ischemia‑reperfusion injury (CIRI). Endoplasmic reticulum stress (ERS) induces apoptosis after CIRI by activating caspase‑12 and the CHOP pathway. The present study aimed to determine whether OXA mitigates CIRI by inhibiting ERS‑induced neuronal apoptosis.

Orexin-A protects against cerebral ischemia-reperfusion injury by inhibiting excessive autophagy through OX1R-mediated MAPK/ERK/mTOR pathway.

Orexin A (OXA) is a neuroprotective peptide that exerts protective effects on multiple physiological and pathological processes. Activation of autophagy is linked to the occurrence of cerebral ischemia-reperfusion injury (CIRI); however, its function remains incompletely understood. In this study, OXA was sought to exert its neuroprotective role by regulating autophagy in oxygen and glucose deprivation and reoxygenation (OGD/R) model and middle cerebral artery occlusion (MCAO) model of rats, and to elucidate the underlying molecular mechanisms.

A method for identifying G protein-coupled receptor dimers and their interfaces.

The G protein-coupled receptor (GPCR) dimer interface plays an important role in the formation and stabilization of the dimer. Therefore, identifying the potential receptor-receptor interface is an important part of studying GPCRs. Various strategies have been employed to study the GPCR dimer interface and explore its functional significance, but experimental methods lack robustness and calculations are laborious.

Role of the Extracellular Signal-Regulated Kinase 1/2 Signaling Pathway in Ischemia-Reperfusion Injury.

Extracellular signal-regulated kinase 1/2 (ERK), an important member of the mitogen-activated protein kinase family, is found in many organisms, and it participates in intracellular signal transduction. Various stimuli induce phosphorylation of ERK and . Phosphorylated ERK moves to the nucleus, activates many transcription factors, regulates gene expression, and controls various physiological processes, finally inducing repair processes or cell death.

Orexin-A protects against oxygen-glucose deprivation/reoxygenation-induced cell damage by inhibiting endoplasmic reticulum stress-mediated apoptosis via the Gi and PI3K signaling pathways.

The neuropeptide orexin-A (OXA) has a neuroprotective effect, acting as an anti-apoptotic factor in response to multiple stimuli. Apoptosis induced by endoplasmic reticulum stress (ERS) underlies oxygen-glucose deprivation and reoxygenation (OGD/R)-induced cell damage, an in vitro model of ischemia/reperfusion injury. However, that OXA inhibits ERS-induced apoptosis in the OGD/R model has not been reported.

The Orexin/Receptor System: Molecular Mechanism and Therapeutic Potential for Neurological Diseases.

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.

Orexin-A protects SH-SY5Y cells against HO-induced oxidative damage via the PI3K/MEK/ERK signaling pathway.

Orexin-A elicits multiple potent effects on a variety of tumor cells via different signaling pathways. However, it is unknown whether it has a neuroprotective effect on SH-SY5Y human neuroblastoma cells. This study investigated the neuroprotective effect of Orexin-A against hydrogen peroxide (HO)-induced oxidative damage in SH-SY5Y cells and the underlying mechanism.