NOX1 triggers ferroptosis and ferritinophagy, contributes to Parkinson's disease.

The progressive loss of dopaminergic neurons in the midbrain is the hallmark of Parkinson's disease (PD). A newly emerging form of lytic cell death, ferroptosis, has been implicated in PD. However, it remains unclear in terms of PD-associated ferroptosis underlying causative genes and effective therapeutic approaches.

Identification and Experimental Validation of Parkinson's Disease with Major Depressive Disorder Common Genes.

Parkinson's disease (PD) is the second most common neurodegenerative disease that affects about 10 million people worldwide. Non-motor and motor symptoms usually accompany PD. Major depressive disorder (MDD) is one of the non-motor manifestations of PD it remains unrecognized and undertreated effectively.

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.

Ghrelin protects against rotenone-induced cytotoxicity: Involvement of mitophagy and the AMPK/SIRT1/PGC1α pathway.

Parkinson's disease (PD) is the second most common neurodegenerative disorder, characterized by the loss of dopaminergic neurons in the substantia nigra and the deposition of Lewy bodies. Mitochondrial dysfunction, oxidative stress, and autophagy dysfunction are involved in the pathogenesis of PD. Ghrelin is a brain-gut peptide that has been reported that protected against 1-methyl-4-phenyl-1,2,3,6- tetrahydropyran (MPTP)/MPP-induced toxic effects.

Apelin-36 Protects HT22 Cells Against Oxygen-Glucose Deprivation/Reperfusion-Induced Oxidative Stress and Mitochondrial Dysfunction by Promoting SIRT1-Mediated PINK1/Parkin-Dependent Mitophagy.

Oxidative stress and mitochondrial dysfunction are involved in cerebral ischemia/reperfusion injury-induced neuronal apoptosis. Mitophagy is the main method to eliminate dysfunctional mitochondria. Apelin-36, a type of neuropeptide, has been reported to exert protective effects in cerebral I/R (I/R) injury, but its precise mechanisms remain to be elucidated.

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.

The Role of Mitophagy in Ischemic Stroke.

Mitochondria are important places for eukaryotes to carry out energy metabolism and participate in the processes of cell differentiation, cell information transmission, and cell apoptosis. Autophagy is a programmed intracellular degradation process. Mitophagy, as a selective autophagy, is an evolutionarily conserved cellular process to eliminate dysfunctional or redundant mitochondria, thereby fine-tuning the number of mitochondria and maintaining energy metabolism.

Regulatory effects of ghrelin on endoplasmic reticulum stress, oxidative stress, and autophagy: Therapeutic potential.

Ghrelin is a regulatory peptide that is the endogenous ligand of the growth hormone secretagogue 1a (GHS-R1a) which belongs to the G protein-coupled receptor family. Ghrelin and GHS-R1a are widely expressed in the central and peripheral tissues and play therapeutic potential roles in the cytoprotection of many internal organs. Endoplasmic reticulum stress (ERS), oxidative stress, and autophagy dysfunction, which are involved in various diseases.

Apelin-13 inhibits apoptosis and excessive autophagy in cerebral ischemia/reperfusion injury.

Apelin-13 is a novel endogenous ligand for an angiotensin-like orphan G-protein coupled receptor, and it may be neuroprotective against cerebral ischemia injury. However, the precise mechanisms of the effects of apelin-13 remain to be elucidated. To investigate the effects of apelin-13 on apoptosis and autophagy in models of cerebral ischemia/reperfusion injury, a rat model was established by middle cerebral artery occlusion.

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.

Ghrelin mitigates MPP-induced cytotoxicity: Involvement of ERK1/2-mediated Nrf2/HO-1 and endoplasmic reticulum stress PERK signaling pathway.

Parkinson's disease (PD) is a common progressive and multifactorial neurodegenerative disease. Current pharmacological therapies for PD are inadequate and often accompanied by serious side effects. In search of neuroprotective agents being considered to be beneficial to PD therapy.

Ghrelin protects dopaminergic neurons against MPTP neurotoxicity through promoting autophagy and inhibiting endoplasmic reticulum mediated apoptosis.

Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder, the important pathology of PD due to the prominent loss of the dopaminergic neurodegeneration in the substantia nigra pars compacta (SNpc) and striatum (STR). Although the etiology of PD is not fully understood, aggregation of α-synuclein, impaired autophagy, and endoplasmic reticulum stress (ERS) are involved in the pathogenesis of PD. Previously it has been demonstrated that Ghrelin is a kind of peptide protected dopaminergic neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyran (MPTP)-induced neurotoxicity, but the detailed mechanism remains to be elucidated.

Roles for heterodimerization of APJ and B2R in promoting cell proliferation via ERK1/2-eNOS signaling pathway.

Apelin receptor (APJ) and bradykinin B2 receptor (B2R) play an important role in many physiological processes and share multiple similar characteristics in distribution and functions in the cardiovascular system. We first identified the endogenous expression of APJ and B2R in human umbilical vein endothelial cells (HUVECs) and their co-localization on human embryonic kidney (HEK) 293 cells membrane. A suite of bioluminescence and fluorescence resonance energy transfer (BRET and FRET), proximity ligation assay (PLA), and co-immunoprecipitation (Co-IP) was exploited to demonstrate formation of functional APJ and B2R heterodimer in HUVECs and transfected cells.

Apelin-36 mediates neuroprotective effects by regulating oxidative stress, autophagy and apoptosis in MPTP-induced Parkinson's disease model mice.

Parkinson's disease (PD), a common human neurodegenerative disorder, is characterized by the presence of intraneuronal Lewy bodies composed principally of abnormal aggregated and post-translationally modified α-synuclein. In our previous research, we have demonstrated the neuroprotective effect of Apelin-36, a neuroendocrine peptide in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP)-lesioned PD model mice. Therefore, this study was designed to evaluate the neuroprotective mechanism of Apelin-36 against MPTP-induced neurotoxicity in mice.

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.

Apelin-36 mitigates MPTP/MPP-induced neurotoxicity: Involvement of α-synuclein and endoplasmic reticulum stress.

Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons within the substantia nigra compacta (SNpc) which leads to the behavioral dysfunction. In the present study, we investigated the effect of Apelin-36 on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP)/1-methyl-4-phenylpyridinium (MPP)-induced neurotoxicity. The treatment with Apelin-36 significantly alleviated the MPTP-induced the behavioral dysfunction and dopaminergic neurodegeneration in the SNpc of mice, and also remarkably decreased the MPP-induced cell death of SH-SY5Y cells.

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.

[Research advances in endogenous neural stem cells promoting neural repair after ischemic stroke].

Neural stem cell therapy, as a new therapeutic method for neural diseases, has aroused a wide concern for over 20 years since neural stem cells were first found in 1992. Ischemic stroke is highly concerned because of its high incidence, mortality and disability rates. Because the brain has a limited ability to repair itself, to improve neural function and promote neural regeneration may help to prevent occurrence and development of neurological diseases.

Apelin-13 protects dopaminergic neurons in MPTP-induced Parkinson's disease model mice through inhibiting endoplasmic reticulum stress and promoting autophagy.

The dopaminergic neurodegeneration in the substantia nigrapars compacta (SNpc) and striatum of the midbrain is the important pathological feature of Parkinson's disease (PD). It has been shown that autophagy and endoplasmic reticulum stress (ERS) are involved in the occurrence and development of PD. The neuropeptide Apelin-13 is neuroprotective in the neurological diseases such as PD, Alzheimer's disease and cerebral ischemic stroke.

Apelin-36 exerts the cytoprotective effect against MPP-induced cytotoxicity in SH-SY5Y cells through PI3K/Akt/mTOR autophagy pathway.

Aims: Parkinson's disease (PD) is a common neurodegenerative disease typically associated with the accumulation of α-synuclein. Autophagy impairment is thought to be involved in the dopaminergic neurodegeneration in PD. We investigate the effect of Apelin-36 on the activated phosphatidylinositol 3-kinase (PI3K)/protein kinase B(Akt)/the mammalian target of rapamycin (mTOR) autophagy pathway in 1-methyl-4-phenylpyridinium (MPP)-treated SH-SY5Y cells, which is involved in the cytoprotective effect of Apelin-36.

Signaling transduction regulated by 5-hydroxytryptamine 1A receptor and orexin receptor 2 heterodimers.

As G-protein-coupled receptors (GPCRs), 5-hydroxytryptamine 1A receptor (5-HT1AR) and orexin receptor 2 (OX2R) regulate the levels of the cellular downstream molecules. The heterodimers of different GPCRs play important roles in various of neurological diseases. Moreover, 5-HT1AR and OX2R are involved in the pathogenesis of neurological diseases such as depression with deficiency of hippocampus plasticity.

Ghrelin Through GHSR1a and OX1R Heterodimers Reveals a Gαs-cAMP-cAMP Response Element Binding Protein Signaling Pathway .

Growth hormone secretagogue receptor 1α (GHSR1a) and Orexin 1 receptor (OX1R) are involved in various important physiological processes, and have many similar characteristics in function and distribution in peripheral tissues and the central nervous system. We explored the possibility of heterodimerization between GHSR1a and OX1R and revealed a signal transduction pathway mechanism. In this study, bioluminescence and fluorescence resonance energy transfer and co-immunoprecipitation (Co-IP) analyses were performed to demonstrate the formation of functional GHSR1a/OX1R heterodimers.

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.