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NadPH AND Parkinsons

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https://www.readbyqxmd.com/read/30195055/reduced-nicotinamide-adenine-dinucleotide-phosphate-inhibits-mptp-induced-neuroinflammation-and-neurotoxicity
#1
Ying Zhou, Junchao Wu, Rui Sheng, Mei Li, Yan Wang, Rong Han, Feng Han, Zhong Chen, Zheng-Hong Qin
It is generally believed that oxidative stress and neuroinflammation are implicated in the pathogenesis of Parkinson's disease (PD). Reduced nicotinamide adenine dinucleotide phosphate (NADPH) has been demonstrated to have potent neuroprotective effects against oxidative stress. In the present research, we investigated if NADPH could offer neuroprotection by inhibiting glia-mediated neuroinflammation induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a mechanism contributing to PD pathogenesis...
September 6, 2018: Neuroscience
https://www.readbyqxmd.com/read/30157869/nod2-promotes-dopaminergic-degeneration-regulated-by-nadph-oxidase-2-in-6-hydroxydopamine-model-of-parkinson-s-disease
#2
Li Cheng, Lin Chen, Xinbing Wei, Yimeng Wang, Zhiping Ren, Shenglan Zeng, Xiumei Zhang, Haitao Wen, Chengjiang Gao, Huiqing Liu
BACKGROUND: In Parkinson's disease (PD), loss of striatal dopaminergic (DA) terminals and degeneration of DA neurons in the substantia nigra (SN) are associated with inflammation. Nucleotide-binding oligomerization domain-containing protein (NOD)2, one of the first discovered NOD-like receptors, plays an important role in inflammation. However, the role of NOD2 has not been elucidated in PD. METHODS: NOD2 mRNA and protein expression in the SN and the striatum of C57BL/6 mice treated with 6-hydroxydopamine (6-OHDA) was measured...
August 29, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/30076526/at2r-activation-prevents-microglia-pro-inflammatory-activation-in-a-nox-dependent-manner-inhibition-of-pkc-activation-and-p47-phox-phosphorylation-by-pp2a
#3
Shahnawaz Ali Bhat, Anika Sood, Rakesh Shukla, Kashif Hanif
Microglia-induced reactive oxygen species (ROS) production and inflammation play an imperative role in neurodegenerative diseases like Alzheimer's disease (AD) and Parkinson's disease (PD). It has been established that angiotensin II type-2 receptor (AT2R) activation is neuroprotective in central nervous system diseases like stroke and AD. However, the involvement of AT2R in NADPH oxidase (NOX)-mediated microglia activation is still elusive. Therefore, the present study investigated the role of AT2R in angiotensin II (Ang II) or Phorbol 12-myristate 13-acetate (PMA)-induced microglia activation in BV2 cells, primary microglia, p47phox knockout (p47KO) microglia, and in vivo...
August 3, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/30051353/loss-of-brain-norepinephrine-elicits-neuroinflammation-mediated-oxidative-injury-and-selective-caudo-rostral-neurodegeneration
#4
Sheng Song, Lulu Jiang, Esteban A Oyarzabal, Belinda Wilson, Zibo Li, Yen-Yu Ian Shih, Qingshan Wang, Jau-Shyong Hong
Environmental toxicant exposure has been strongly implicated in the pathogenesis of Parkinson's disease (PD). Clinical manifestations of non-motor and motor symptoms in PD stem from decades of progressive neurodegeneration selectively afflicting discrete neuronal populations along a caudo-rostral axis. However, recapitulating this spatiotemporal neurodegenerative pattern in rodents has been unsuccessful. The purpose of this study was to generate such animal PD models and delineate mechanism underlying the ascending neurodegeneration...
July 27, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29987762/angiotensin-type-1-receptor-antagonists-protect-against-alpha-synuclein-induced-neuroinflammation-and-dopaminergic-neuron-death
#5
Ana I Rodriguez-Perez, Diego Sucunza, Maria A Pedrosa, Pablo Garrido-Gil, Jaime Kulisevsky, Jose L Lanciego, Jose L Labandeira-Garcia
The loss of dopaminergic neurons and α-synuclein accumulation are major hallmarks of Parkinson's disease (PD), and it has been suggested that a major mechanism of α-synuclein toxicity is microglial activation. The lack of animal models that properly reproduce PD, and particularly the underlying synucleinopathy, has hampered the clarification of PD mechanisms and the development of effective therapies. Here, we used neurospecific adeno-associated viral vectors serotype 9 coding for either the wild-type or mutated forms of human alpha-synuclein (WT and SynA53T, respectively) under the control of a synapsin promoter to further induce a marked dopaminergic neuron loss together with an important microglial neuroinflammatory response...
July 9, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29872377/simvastatin-inhibits-activation-of-nadph-oxidase-p38-mapk-pathway-and-enhances-expression-of-antioxidant-protein-in-parkinson-disease-models
#6
Huichun Tong, Xiuping Zhang, Xingjun Meng, Lingli Lu, Dongmei Mai, Shaogang Qu
Evidence suggests that oxidative stress is involved in the pathogenesis of Parkinson disease (PD). Simvastatin has been suggested to protect against oxidative stress in several diseases. However, the molecular mechanisms by which simvastatin protects against neuropathology and oxidative damage in PD are poorly elucidated. In this study, we aimed to investigate the potential neuroprotective effects of simvastatin owing to its anti-oxidative properties in 6-hydroxydopamine (6-OHDA)-treated SH-SY5Y cells and mice...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29769744/nadph-ameliorates-mptp-induced-dopaminergic-neurodegeneration-through-inhibiting-p38mapk-activation
#7
Jing-Si Zhou, Zhou Zhu, Feng Wu, Ying Zhou, Rui Sheng, Jun-Chao Wu, Zheng-Hong Qin
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+ ...
May 16, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29665408/neuroprotective-effect-of-angiotensin-1-7-against-rotenone-induced-oxidative-damage-in-cath-a-neurons
#8
Yong Zhou, Min Li, Dong-Lin Zhu, Teng Jiang, Qing Gao, Xiao-Hong Tang, Shu-Gang Zhang, Jie Lu, Ying-Dong Zhang
There is evidence to support that ROSs are increased in Parkinson's disease (PD). Our recent research showed that angiotensin II (Ang II) participated in the pathogenesis of PD by triggering oxidative stress. Angiotensin-(1-7)[Ang-(1-7)] has been shown to moderate the adverse effects of the Ang II in many diseases. The purpose of the present study was to determine whether the Ang-(1-7) could have similar effects in CATH.a neurons. We used rotenone-induced neuron injury models to evaluate changes in cultured CATH...
August 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29568078/taurine-protects-dopaminergic-neurons-in-a-mouse-parkinson-s-disease-model-through-inhibition-of-microglial-m1-polarization
#9
Yuning Che, Liyan Hou, Fuqiang Sun, Cong Zhang, Xiaofang Liu, Fengyuan Piao, Dan Zhang, Huihua Li, Qingshan Wang
Microglia-mediated neuroinflammation is implicated in multiple neurodegenerative disorders, including Parkinson's disease (PD). Hence, the modulatioein of sustained microglial activation may have therapeutic potential. This study is designed to test the neuroprotective efficacy of taurine, a major intracellular free β-amino acid in mammalian tissues, by using paraquat and maneb-induced PD model. Results showed that mice intoxicated with paraquat and maneb displayed progressive dopaminergic neurodegeneration and motor deficits, which was significantly ameliorated by taurine...
April 1, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29508060/taurine-protects-noradrenergic-locus-coeruleus-neurons-in-a-mouse-parkinson-s-disease-model-by-inhibiting-microglial-m1-polarization
#10
Liyan Hou, Yuning Che, Fuqiang Sun, Qingshan Wang
Beyond nigrostriatal dopaminergic system, the noradrenergic locus coeruleus (LC/NE) neurons are also degenerated in patients with Parkinson's disease (PD), the second most common neurodegenerative disorder. We previously reported that microglia-mediated neuroinflammation contributes to LC/NE neurodegeneration. The purpose of this study is aimed to test whether taurine, an endogenous amino acid, could be able to protect LC/NE neurons through inhibition of microglial activation using paraquat and maneb-induced mouse PD model...
May 2018: Amino Acids
https://www.readbyqxmd.com/read/29428223/angiotensin-1-7-ameliorates-6-hydroxydopamine-lesions-in-hemiparkinsonian-rats-through-activation-of-mas-receptor-pi3k-akt-bdnf-pathway-and-inhibition-of-angiotensin-ii-type-1-receptor-nf-%C3%AE%C2%BAb-axis
#11
Mostafa A Rabie, Mai A Abd El Fattah, Noha N Nassar, Hanan S El-Abhar, Dalaal M Abdallah
MAS receptor (MASR), expressed in several brain areas, conferred neuroprotection against neurodegenerative disorders when activated by angiotensin (Ang) 1-7; however, its role in Parkinson's disease (PD) remains elusive. Intra-striatal post-administration of Ang1-7, using a 6-hydroxydopamine (OHDA) PD model, improved motor performance and muscle coordination. On the molecular level, Ang1-7 upregulated the striatal expression of MASR and caused upsurge in its downstream targets (p-PI3K/p-Akt/p-CREB/BDNF) to phosphorylate TrKB, which in a positive feedback upregulates MASR...
May 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29352205/2-5-hexanedione-induces-dopaminergic-neurodegeneration-through-integrin-%C3%AE-m-%C3%AE-2-nadph-oxidase-axis-mediated-microglial-activation
#12
Cong Zhang, Liyan Hou, Jie Yang, Yuning Che, Fuqiang Sun, Huihua Li, Qingshan Wang
Recent study demonstrated that chronic exposure to solvents increases the risk of Parkinson's disease (PD), the second most common neurodegenerative disorder characterized by progressive dopaminergic neurodegeneration in the substantia nigra (SN). n-Hexane, a widely used organic solvent, displays central-peripheral neurotoxicity, which is mainly mediated by its active metabolite, 2,5-hexanedione (HD). However, whether HD exposure contributes to PD remains unclear. In this study, we found that rats exposed to HD displayed progressive dopaminergic neurodegeneration in the nigrostriatal system...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29287724/paris-reprograms-glucose-metabolism-by-hif-1%C3%AE-induction-in-dopaminergic-neurodegeneration
#13
Hojin Kang, Areum Jo, Hyein Kim, Rin Khang, Ji-Yeong Lee, Hanna Kim, Chi-Hu Park, Jeong-Yun Choi, Yunjong Lee, Joo-Ho Shin
Our previous study found that PARIS (ZNF746) transcriptionally suppressed transketolase (TKT), a key enzyme in pentose phosphate pathway (PPP) in the substantia nigra (SN) of AAV-PARIS injected mice. In this study, we revealed that PARIS overexpression reprogrammed glucose metabolic pathway, leading to the increment of glycolytic proteins along with TKT reduction in the SN of AAV-PARIS injected mice. Knock-down of TKT in differentiated SH-SY5Y cells led to an increase of glycolytic enzymes and decrease of PPP-related enzymes whereas overexpression of TKT restored PARIS-mediated glucose metabolic shift, suggesting that glucose metabolic alteration by PARIS is TKT-dependent...
January 22, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29286084/petasites-japonicus-bakkenolide-b-inhibits-lipopolysaccharide%C3%A2-induced-pro%C3%A2-inflammatory-cytokines-via-ampk-nrf2-induction-in-microglia
#14
Sun Young Park, Min Hyun Choi, Geuntae Park, Young-Whan Choi
Abnormal neuroinflammatory responses have diverse roles in neuronal death, oxidative stress and neurodegenerative diseases, such as Alzheimer's and Parkinson's disease. Microglia regulate these responses via molecular signaling cascades that involve inflammatory cytokines and complement proteins. Bakkenolide B from Petasites japonicus exhibits significant anti‑inflammatory and anti‑allergic bioactivities. The present study investigated the anti‑neuroinflammatory effects and underlying molecular mechanisms of bakkenolide B on the lipopolysaccharide (LPS)‑mediated neuroinflammatory response in microglia...
March 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29170000/sleep-disorder-and-altered-locomotor-activity-as-biomarkers-of-the-parkinson-s-disease-cholinopathy-in-rat
#15
Jelena Ciric, Katarina Lazic, Slobodan Kapor, Milka Perovic, Jelena Petrovic, Vesna Pesic, Selma Kanazir, Jasna Saponjic
In order to find out the possible earliest biomarkers of Parkinson's disease (PD) cholinopathy, we followed the impact of bilateral pedunculopontine tegmental nucleus (PPT) lesion in rat on: the cortical and hippocampal sleep/wake states architectures, all sleep states related EEG microstructures, sleep spindles, the basal and stimulated locomotor activity. Sleep and basal locomotor activity in adult Wistar rats were followed during their inactive circadian phase, and throughout the same aging period. The bilateral PPT lesions were done by 0...
February 26, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29154191/integrin-cd11b-mediates-%C3%AE-synuclein-induced-activation-of-nadph-oxidase-through-a-rho-dependent-pathway
#16
Liyan Hou, Xiuqi Bao, Caixia Zang, Hanyu Yang, Fuqiang Sun, Yuning Che, Xuefei Wu, Shao Li, Dan Zhang, Qingshan Wang
The activation of microglial NADPH oxidase (NOX2) induced by α-synuclein has been implicated in Parkinson's disease (PD) and other synucleinopathies. However, how α-synuclein activates NOX2 remains unclear. Previous study revealed that both toll-like receptor 2 (TLR2) and integrin play important roles in α-synuclein-induced microglial activation. In this study, we found that blocking CD11b, the α chain of integrin αM β2 , but not TLR2 attenuated α-synuclein-induced NOX2 activation in microglia. The involvement of CD11b in α-synuclein-induced activation of NOX2 was further confirmed in CD11b-/- microglia by showing reduced membrane translocation of NOX2 cytosolic subunit p47phox and superoxide production...
April 2018: Redox Biology
https://www.readbyqxmd.com/read/29132391/nadph-oxidases-in-parkinson-s-disease-a-systematic-review
#17
REVIEW
Karim Belarbi, Elodie Cuvelier, Alain Destée, Bernard Gressier, Marie-Christine Chartier-Harlin
Parkinson's disease (PD) is a progressive movement neurodegenerative disease associated with a loss of dopaminergic neurons in the substantia nigra of the brain. Oxidative stress, a condition that occurs due to imbalance in oxidant and antioxidant status, is thought to play an important role in dopaminergic neurotoxicity. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are multi-subunit enzymatic complexes that generate reactive oxygen species as their primary function. Increased immunoreactivities for the NADPH oxidases catalytic subunits Nox1, Nox2 and Nox4 have been reported in the brain of PD patients...
November 13, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29067118/tectorigenin-attenuates-the-mpp-induced-sh-sy5y-cell-damage-indicating-a-potential-beneficial-role-in-parkinson-s-disease-by-oxidative-stress-inhibition
#18
Ping Gong, Fang Deng, Wei Zhang, Jin Ji, Jia Liu, Yinan Sun, Jiayu Hu
Tectorigenin is a plant isoflavonoid primarily derived from the flowers of Pueraria thomsonii Benth. Although various biological properties of tectorigenin have been reported, such as its antioxidant activity, the effects of tectorigenin on the cellular models of Parkinson's disease have not yet been elucidated. The aims of the current study were to investigate whether tectorigenin prevents neurotoxicity induced by MPP+ (also known as 1-methyl-4-phenylpyridinium) in SH-SY5Y cells and to elucidate the underlying protective mechanism...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29027056/curcumin-affords-neuroprotection-and-inhibits-%C3%AE-synuclein-aggregation-in-lipopolysaccharide-induced-parkinson-s-disease-model
#19
Neha Sharma, Bimla Nehru
Parkinson's disease (PD) pathology is characterized by the abnormal accumulation and aggregation of the pre-synaptic protein α-synuclein in the dopaminergic neurons as Lewy bodies (LBs). Curcumin, which plays a neuroprotective role in various animal models of PD, was found to directly modulate the aggregation of α-synuclein in in vitro as well as in in vivo studies. While curcumin has been shown to exhibit strong anti-oxidant and anti-inflammatory properties, there are a number of other possible mechanisms by which curcumin may alter α-synuclein aggregation which still remains obscure...
April 2018: Inflammopharmacology
https://www.readbyqxmd.com/read/28985560/ferroptosis-a-regulated-cell-death-nexus-linking-metabolism-redox-biology-and-disease
#20
REVIEW
Brent R Stockwell, José Pedro Friedmann Angeli, Hülya Bayir, Ashley I Bush, Marcus Conrad, Scott J Dixon, Simone Fulda, Sergio Gascón, Stavroula K Hatzios, Valerian E Kagan, Kay Noel, Xuejun Jiang, Andreas Linkermann, Maureen E Murphy, Michael Overholtzer, Atsushi Oyagi, Gabriela C Pagnussat, Jason Park, Qitao Ran, Craig S Rosenfeld, Konstantin Salnikow, Daolin Tang, Frank M Torti, Suzy V Torti, Shinya Toyokuni, K A Woerpel, Donna D Zhang
Ferroptosis is a form of regulated cell death characterized by the iron-dependent accumulation of lipid hydroperoxides to lethal levels. Emerging evidence suggests that ferroptosis represents an ancient vulnerability caused by the incorporation of polyunsaturated fatty acids into cellular membranes, and cells have developed complex systems that exploit and defend against this vulnerability in different contexts. The sensitivity to ferroptosis is tightly linked to numerous biological processes, including amino acid, iron, and polyunsaturated fatty acid metabolism, and the biosynthesis of glutathione, phospholipids, NADPH, and coenzyme Q10 ...
October 5, 2017: Cell
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