δ-Opioid receptor activation reduces α-synuclein overexpression and oligomer formation induced by MPP+ and/or hypoxia

Chen, Tao; Li, Jessica; Chao, Dongman; Sandhu, Harleen K.; Liao, Xiao‐Ping; Zhao, Jianlong; Wen, Guoqiang; Xia, Ying

doi:10.1016/j.expneurol.2014.02.022

Cited by 44 publications

(31 citation statements)

References 52 publications

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“…This effect may be beneficial for the prevention of DA neuron damage in an aged brain with hypoxic/ischemic injury. More recently, we found direct evidence from in vitro PD models showing that DOR activation has an antiparkinsonism effect with a beneficial regulation of cellular and molecular signaling . Mabrouk et al have also found that DOR activation may be a useful target for symptomatic treatment of PD in humans These data from our studies and those of others strongly suggest that DOR system may be a target for PD treatment.…”

Section: Introductionsupporting

confidence: 81%

“…Indeed, our data from a transgenic model suggest that the DOR system is injured before the occurrence of PD behavior (unpublished data). More recently, we have performed mechanistic studies with in vitro PD models and demonstrated that DOR activation has an antiparkinsonism effect via specific mechanisms …”

Section: Dor: a Potential Protector Against Pdmentioning

confidence: 99%

“…Note that DOR attenuated ɑ‐synuclein overexpression induced by hypoxia and MPP+. Cited from Chen et al…”

Section: Potential Mechanisms For Dor Protection Against Pdmentioning

confidence: 99%

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The delta‐opioid receptor and Parkinson’s disease

Huang

Ren

et al. 2018

CNS Neurosci Ther

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Parkinson's disease (PD) is a common degenerative neurological disease leading to a series of familial, medical, and social problems. Although it is known that the major characteristics of PD pathophysiology are the dysfunction of basal ganglia due to injury/loss of dopaminergic neurons in the substantia nigra pars compacta dopaminergic and exhaustion of corpus striatum dopamine, therapeutic modalities for PD are limited in clinical settings up to date. It is of utmost importance to better understand PD pathophysiology and explore new solutions for this serious neurodegenerative disorder. Our recent work and those of others suggest that the delta-opioid receptor (DOR) is neuroprotective and serves an antiparkinsonism role in the brain. This review summarizes recent progress in this field and explores potential mechanisms for DOR-mediated antiparkinsonism.

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Section: Introductionsupporting

confidence: 81%

Section: Dor: a Potential Protector Against Pdmentioning

confidence: 99%

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The delta‐opioid receptor and Parkinson’s disease

Huang

Ren

et al. 2018

CNS Neurosci Ther

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“…Thirdly, a recent study using absolute quantitative real‐time RT‐PCR showed that the kidney was, in terms of the opioid receptors, predominantly a ‘DOR tissue’ because DOR expression was almost 45‐fold higher than that of KOR, with no detectable expression of MORs (Peng et al ., ). Indeed, the present study and another independent study in our laboratory (Chen et al ., ) have detected DOR expression at both mRNA and protein levels. Therefore, this cell line is ideal for exploring the role of DOR in the regulation of Nrf2, as a first step.…”

Section: Discussionmentioning

confidence: 99%

“…We and others have demonstrated that the δ‐opioid receptor (DOR) mediates responses to stressful stimuli, such as hypoxia and ischaemia, and activation of DOR is cytoprotective against hypoxic/ischaemic injury in various in vitro and in vivo tissue and cell sources, including primary cultured neuron (Zhang et al ., ), HEK293t cells (Chen et al ., ), PC12 cells (Wang et al ., ) and intact animals (Borlongan et al ., ; Yang et al ., ; Johnson and Turner, ; Staples et al ., ; Tian et al ., ). One of the potential mechanisms underlying DOR neuroprotection is related to its ability to attenuate ROS oxidative stress and increase antioxidant capacity in the ischaemic brain (Yang et al ., ).…”

Section: Introductionmentioning

confidence: 99%

A novel mechanism for cytoprotection against hypoxic injury: δ‐opioid receptor‐mediated increase in Nrf2 translocation

Cao

Chao²,

Zhou

et al. 2015

British J Pharmacology

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BACKGROUND AND PURPOSEHypoxia/reoxygenation induces synthesis of reactive oxygen species (ROS) which can attack macromolecules and cause brain injury. The transcription factor, nuclear factor (erythroid-derived 2)-like 2, (Nrf2), ia potent activator of genes with an antioxidant responsive element and Nrf2 can counteract oxidative injury by increasing expression of several antioxidative genes in response to ROS stress. Here, we show that activation of the δ-opioid receptor (DOR) increasedNrf2 protein expression and translocation, thereby leading to cytoprotection. EXPERIMENTAL APPROACHWe used HEK293t cells exposed to 0.5% O2 for 16 h and then reoxygenated for 4 h as a model of hypoxia-reperfusion (H/R) injury. Real time PCR, Western blotting, siRNA and immunohistochemical techniques were used to follow Nrf2 expression and activity. Cell viability and damage (as LDH leakage) were also measured. KEY RESULTSH/R injury triggered Nrf2 translocation into the nucleus and up-regulated expression of several downstream genes, relevant to antioxidation, such as NAD(P)H:quinone oxidoreductase (NQO1). Incubation with the DOR agonist UFP-512 enhanced Nrf2 protein expression and translocation and up-regulated its downstream genes in normoxia and further increased Nrf2 expression and translocation after H/R, protecting the cells against loss of viability and damage. The effect of UFP-512 on Nrf2 nuclear translocation was blocked by the DOR antagonist, naltrindole. Also, DOR-mediated cytoprotection was strongly inhibited after transfection of HEK293t cells with Nrf2 siRNA. CONCLUSIONS AND IMPLICATIONSThe DOR agonist UFP-512 was cytoprotective against H/R injury and this effect was partly dependent on DOR-mediated increase in Nrf2 function. AbbreviationsARE, antioxidant response element; DOR, δ-opioid receptor; GCLC, glutamate-cysteine ligase-catalytic subunit; GCLM, glutamate-cysteine ligase-modifier subunit; H/R, hypoxia-reperfusion; HO-1, haem oxygenase 1; Keap1, Kelch-like ECH associating protein 1; NQO1, NAD(P)H dehydrogenase [quinone] 1; Nrf2, nuclear factor (erythroid-derived 2)-like 2; ROS, reactive oxygen species; siRNA, small interfering RNA

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Plasma α‐synuclein levels are increased in patients with obstructive sleep apnea syndrome

Sun

Chen

et al. 2019

Ann Clin Transl Neurol

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Objective Obstructive sleep apnea syndrome ( OSAS ) is characterized by nocturnal intermittent hypoxemia and can increase the risk of Parkinson's disease. This study aimed to investigate the association between plasma α ‐synuclein levels and hypoxia in the patients with OSAS . Methods We recruited 42 OSAS patients and 46 controls with simple snoring matched for age and gender. OSAS was diagnosed on the basis of the clinical symptoms as well as the nighttime polysomnography. Plasma total α ‐synuclein and phosphorylated α ‐synuclein levels were measured by ELISA kits. Results The OSAS patients had significant higher levels of plasma total α ‐synuclein and phosphorylated α ‐synuclein levels. Both of the above indexes were positively correlated with the apnea–hypopnea index and the oxygen desaturation index, while they were negatively correlated with the mean and lowest oxyhemoglobin saturations. Interpretation This study suggests that chronic intermittent hypoxia can increase the α ‐synuclein levels, which may contribute to the pathogenesis of Parkinson's disease.

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δ-Opioid receptor activation reduces α-synuclein overexpression and oligomer formation induced by MPP+ and/or hypoxia

Cited by 44 publications

References 52 publications

The delta‐opioid receptor and Parkinson’s disease

The delta‐opioid receptor and Parkinson’s disease

A novel mechanism for cytoprotection against hypoxic injury: δ‐opioid receptor‐mediated increase in Nrf2 translocation

Plasma α‐synuclein levels are increased in patients with obstructive sleep apnea syndrome

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