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Title:
NADPH ameliorates MPTP-induced dopaminergic neurodegeneration through inhibiting p38MAPK activation | Acta Pharmacologica Sinica
Description:
Parkinson’s disease (PD) is the second most common neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in substantia nigra pars compacta (SNpc). Although the pathogenic mechanism underlying PD remains largely unknown, decreased nigral glutathione (GSH) in postmortem brains of PD patients supports the presence of oxidative stress in PD. We found that Nicotinamide adenine dinucleotide phosphate (NADPH), which is important for maintaining the level of GSH, protected dopaminergic (DA) neurons from neurotoxicity of MPTP/MPP+. In the present study, NADPH prevented DA neurons from MPTP toxicity with increased GSH and decreased reactive oxygen species (ROS) levels in the ventral midbrain of mice, and improved motor activity. Our present results demonstrated that NADPH inhibited the phosphorylation of p38MAPK, decreased the level of TP53 protein, and inhibited TP53 nuclear translocation in DA neurons of SNpc and in MES23.5 cells. Furthermore, NADPH decreased the protein level of TP53 target gene, Bax, cleavage of PARP, and nuclei condensation. Taken together, NADPH abrogated MPTP-induced p38MAPK phosphorylation, TP53 nuclear translocation, and Bax induction, and finally, MPTP/MPP+-induced apoptosis of DA neurons. This study suggests that NADPH may be a novel therapeutic candidate for PD.
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pubmed, article, google, scholar, cas, disease, parkinsons, central, nature, nadph, zhou, model, wang, neurons, apoptosis, cell, content, oxidative, stress, dopaminergic, med, pathway, acta, glutathione, mitochondrial, res, zhang, cookies, data, activation, qin, mptp, protein, access, free, sun, role, chen, biol, kim, signaling, effects, privacy, zhu, decreased, study, cells, open, parkinson, death,
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nature portfolio permissions reprints privacy policy translational research nature advertising acta pharmacologica sinica social media inhibiting ask1/p38mapk pathway zheng-hong qin mitogen-activated protein kinases tp53 nuclear translocation single-cell genomic profiling pentose-phosphate pathway disruption double-blind safety trial microrna-181a–2–3p shuttled ischemia/reperfusion-induced upregulation cell line data mptp/mpp+-induced apoptosis reactive oxygen species jackson-lewis vr kinase signaling pathways p53-inducible regulator ofglycolysis pro-apoptotic protein bax inhibiting p38mapk activation author correspondence tigar-regulated metabolic pathway permissions related mitochondrion pathway biochim biophys acta programmed cell death compromised mapk signaling acta pharmacol sin jing-si zhou mitochondria- dependent mechanism dopaminergic cell line p38 mapk induced p53 signaling pathway substantia nigra origin mptp-induced neurotoxicity primate nigrostriatal atlas gene delivery system 9-mediated apoptotic pathways personal data data protection impulse control disorders china contrast-induced nephropathy privacy mitochondrial death functions
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- Glutathione Glutathione and Parkinson's disease: is this the elephant in the room?
- Mitogen-activated protein kinases and reactive oxygen species: how can ros activate MAPK pathways?
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headline:NADPH ameliorates MPTP-induced dopaminergic neurodegeneration through inhibiting p38MAPK activation
description:Parkinsonâs disease (PD) is the second most common neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in substantia nigra pars compacta (SNpc). Although the pathogenic mechanism underlying PD remains largely unknown, decreased nigral glutathione (GSH) in postmortem brains of PD patients supports the presence of oxidative stress in PD. We found that Nicotinamide adenine dinucleotide phosphate (NADPH), which is important for maintaining the level of GSH, protected dopaminergic (DA) neurons from neurotoxicity of MPTP/MPP+. In the present study, NADPH prevented DA neurons from MPTP toxicity with increased GSH and decreased reactive oxygen species (ROS) levels in the ventral midbrain of mice, and improved motor activity. Our present results demonstrated that NADPH inhibited the phosphorylation of p38MAPK, decreased the level of TP53 protein, and inhibited TP53 nuclear translocation in DA neurons of SNpc and in MES23.5 cells. Furthermore, NADPH decreased the protein level of TP53 target gene, Bax, cleavage of PARP, and nuclei condensation. Taken together, NADPH abrogated MPTP-induced p38MAPK phosphorylation, TP53 nuclear translocation, and Bax induction, and finally, MPTP/MPP+-induced apoptosis of DA neurons. This study suggests that NADPH may be a novel therapeutic candidate for PD.
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headline:NADPH ameliorates MPTP-induced dopaminergic neurodegeneration through inhibiting p38MAPK activation
description:Parkinsonâs disease (PD) is the second most common neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in substantia nigra pars compacta (SNpc). Although the pathogenic mechanism underlying PD remains largely unknown, decreased nigral glutathione (GSH) in postmortem brains of PD patients supports the presence of oxidative stress in PD. We found that Nicotinamide adenine dinucleotide phosphate (NADPH), which is important for maintaining the level of GSH, protected dopaminergic (DA) neurons from neurotoxicity of MPTP/MPP+. In the present study, NADPH prevented DA neurons from MPTP toxicity with increased GSH and decreased reactive oxygen species (ROS) levels in the ventral midbrain of mice, and improved motor activity. Our present results demonstrated that NADPH inhibited the phosphorylation of p38MAPK, decreased the level of TP53 protein, and inhibited TP53 nuclear translocation in DA neurons of SNpc and in MES23.5 cells. Furthermore, NADPH decreased the protein level of TP53 target gene, Bax, cleavage of PARP, and nuclei condensation. Taken together, NADPH abrogated MPTP-induced p38MAPK phosphorylation, TP53 nuclear translocation, and Bax induction, and finally, MPTP/MPP+-induced apoptosis of DA neurons. This study suggests that NADPH may be a novel therapeutic candidate for PD.
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