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NadPH AND Parkinsons

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https://www.readbyqxmd.com/read/29027056/curcumin-affords-neuroprotection-and-inhibits-%C3%AE-synuclein-aggregation-in-lipopolysaccharide-induced-parkinson-s-disease-model
#1
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...
October 12, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28985560/ferroptosis-a-regulated-cell-death-nexus-linking-metabolism-redox-biology-and-disease
#2
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
https://www.readbyqxmd.com/read/28978491/complement-receptor-3-mediates-nadph-oxidase-activation-and-dopaminergic-neurodegeneration-through-a-src-erk-dependent-pathway
#3
Liyan Hou, Ke Wang, Cong Zhang, Fuqiang Sun, Yuning Che, Xiulan Zhao, Dan Zhang, Huihua Li, Qingshan Wang
Microglial NADPH oxidase (Nox2) plays a key role in chronic neuroinflammation and related dopaminergic neurodegeneration in Parkinson's disease (PD). However, the mechanisms behind Nox2 activation remain unclear. Here, we revealed the critical role of complement receptor 3 (CR3), a microglia-specific pattern recognition receptor, in Nox2 activation and subsequent dopaminergic neurodegeneration by using paraquat and maneb-induced PD model. Suppression or genetic deletion of CR3 impeded paraquat and maneb-induced activation of microglial Nox2, which was associated with attenuation of dopaminergic neurodegeneration...
September 27, 2017: Redox Biology
https://www.readbyqxmd.com/read/28941592/dysregulation-of-serum-nadph-oxidase1-and-ferritin-levels-provides-insights-into-diagnosis-of-parkinson-s-disease
#4
Mohsen Hemmati-Dinarvand, Ali-Akbar Taher-Aghdam, Ali Mota, Sepideh Zununi Vahed, Nasser Samadi
OBJECTIVE: Parkinson's disease (PD) is a common neurodegenerative disease. Oxidative stress is considered as a key modulator in the development of PD. This study aimed to investigate associations between serum NOX1 (NADPH oxidase1), ferritin, selenium (Se) and uric acid (UA) levels and clinical parameters in patients with PD. DESIGN AND METHODS: Serum levels of NOX1, ferritin, Se and UA were measured in 40 PD patients and 40 healthy individuals. Receiver operating characteristic (ROC) analysis was performed to investigate incremental diagnostic value of each factor in the study groups...
September 20, 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/28698499/molecular-mechanisms-behind-free-radical-scavengers-function-against-oxidative-stress
#5
REVIEW
Fereshteh Ahmadinejad, Simon Geir Møller, Morteza Hashemzadeh-Chaleshtori, Gholamreza Bidkhori, Mohammad-Saeid Jami
Accumulating evidence shows that oxidative stress is involved in a wide variety of human diseases: rheumatoid arthritis, Alzheimer's disease, Parkinson's disease, cancers, etc. Here, we discuss the significance of oxidative conditions in different disease, with the focus on neurodegenerative disease including Parkinson's disease, which is mainly caused by oxidative stress. Reactive oxygen and nitrogen species (ROS and RNS, respectively), collectively known as RONS, are produced by cellular enzymes such as myeloperoxidase, NADPH-oxidase (nicotinamide adenine dinucleotide phosphate-oxidase) and nitric oxide synthase (NOS)...
July 10, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28642128/immunomodulation-of-parkinson-s-disease-using-mucuna-pruriens-mp
#6
REVIEW
Sachchida Nand Rai, Hareram Birla, Walia Zahra, Saumitra Sen Singh, Surya Pratap Singh
Immune control is associated with nigrostriatal neuroprotection for Parkinson's disease (PD); though its direct cause and effect relationships have not yet been realized and modulating the immune system for therapeutic gain has been openly discussed. While the pathobiology of PD remains in study, neuroinflammation is thought to speed nigrostriatal degeneration. The neuroinflammatory cascade associated with PD begins with aggregation of misfolded or post-translationally modified α-synuclein (α-syn). Such aggregation results in neuronal cell death and the presence of chronically activated glia (microglia and astroglia), leading to the production of proinflammatory cytokines like tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, and enzymes such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and cyclooxygenase-2 (COX-2)...
June 19, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28538683/metabolic-investigations-of-the-molecular-mechanisms-associated-with-parkinson-s-disease
#7
REVIEW
Robert Powers, Shulei Lei, Annadurai Anandhan, Darrell D Marshall, Bradley Worley, Ronald L Cerny, Eric D Dodds, Yuting Huang, Mihalis I Panayiotidis, Aglaia Pappa, Rodrigo Franco
Parkinson's disease (PD) is a neurodegenerative disorder characterized by fibrillar cytoplasmic aggregates of α-synuclein (i.e., Lewy bodies) and the associated loss of dopaminergic cells in the substantia nigra. Mutations in genes such as α-synuclein (SNCA) account for only 10% of PD occurrences. Exposure to environmental toxicants including pesticides and metals (e.g., paraquat (PQ) and manganese (Mn)) is also recognized as an important PD risk factor. Thus, aging, genetic alterations, and environmental factors all contribute to the etiology of PD...
May 24, 2017: Metabolites
https://www.readbyqxmd.com/read/28527958/treadmill-exercise-produces-neuroprotective-effects-in-a-murine-model-of-parkinson-s-disease-by-regulating-the-tlr2-myd88-nf-%C3%AE%C2%BAb-signaling-pathway
#8
Jung-Hoon Koo, Yong-Chul Jang, Dong-Ju Hwang, Hyun-Seob Um, Nam-Hee Lee, Jae-Hoon Jung, Joon-Yong Cho
Parkinson's disease (PD) is characterized by progressive dopamine depletion and a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Treadmill exercise is a promising non-pharmacological approach for reducing the risk of PD and other neuroinflammatory disorders, such as Alzheimer's disease. The goal of this study was to investigate the effects of treadmill exercise on α-synuclein-induced neuroinflammation and neuronal cell death in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD...
May 18, 2017: Neuroscience
https://www.readbyqxmd.com/read/28385921/the-effects-of-physical-exercise-on-non-motor-symptoms-and-on-neuroimmune-rage-network-in-experimental-parkinsonism
#9
Sofia D Viana, Inês R Pita, Cristina Lemos, Daniel Rial, Patrícia Couceiro, Paulo Rodrigues-Santos, Francisco Caramelo, Félix Carvalho, Syed F Ali, Rui D Prediger, Carlos A Fontes Ribeiro, Frederico C Pereira
Parkinson's disease (PD) prodromic stages comprise neuropsychiatric perturbations that critically compromise patient's quality of life. These non-motor symptoms (NMS) are associated with exacerbated innate immunity, a hallmark of overt PD. Physical exercise (PE) has the potential to improve neuropsychiatric deficits and to modulate immune network including receptors for advanced glycation endproducts (RAGE) and Toll-like receptors (TLRs) in distinct pathological settings. Accordingly, the present study aimed to test the hypothesis that PE i) alleviates PD NMS and ii) modulates neuroimmune RAGE-network in experimental PD...
April 6, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28283350/ultrafine-carbon-particles-promote-rotenone-induced-dopamine-neuronal-loss-through-activating-microglial-nadph-oxidase
#10
Yinxi Wang, Dan Liu, Huifeng Zhang, Yixin Wang, Ling Wei, Yutong Liu, Jieying Liao, Hui-Ming Gao, Hui Zhou
BACKGROUND: Atmospheric ultrafine particles (UFPs) and pesticide rotenone were considered as potential environmental risk factors for Parkinson's disease (PD). However, whether and how UFPs alone and in combination with rotenone affect the pathogenesis of PD remains largely unknown. METHODS: Ultrafine carbon black (ufCB, a surrogate of UFPs) and rotenone were used individually or in combination to determine their roles in chronic dopaminergic (DA) loss in neuron-glia, and neuron-enriched, mix-glia cultures...
May 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28255166/capsaicin-prevents-degeneration-of-dopamine-neurons-by-inhibiting-glial-activation-and-oxidative-stress-in-the-mptp-model-of-parkinson-s-disease
#11
Young C Chung, Jeong Y Baek, Sang R Kim, Hyuk W Ko, Eugene Bok, Won-Ho Shin, So-Yoon Won, Byung K Jin
The effects of capsaicin (CAP), a transient receptor potential vanilloid subtype 1 (TRPV1) agonist, were determined on nigrostriatal dopamine (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD). The results showed that TRPV1 activation by CAP rescued nigrostriatal DA neurons, enhanced striatal DA functions and improved behavioral recovery in MPTP-treated mice. CAP neuroprotection was associated with reduced expression of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) and reactive oxygen species/reactive nitrogen species from activated microglia-derived NADPH oxidase, inducible nitric oxide synthase or reactive astrocyte-derived myeloidperoxidase...
March 3, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28237879/nadph-oxidase-derived-h2o2-mediates-the-regulatory-effects-of-microglia-on-astrogliosis-in-experimental-models-of-parkinson-s-disease
#12
Liyan Hou, Xueying Zhou, Cong Zhang, Ke Wang, Xiaofang Liu, Yuning Che, Fuqiang Sun, Huihua Li, Qingshan Wang, Dan Zhang, Jau-Shyong Hong
Astrogliosis has long been recognized in Parkinson's disease (PD), the most common neurodegenerative movement disorder. However, the mechanisms of how astroglia become activated remain unclear. Reciprocal interactions between microglia and astroglia play a pivotal role in regulating the activities of astroglia. The purpose of this study is to investigate the mechanism by which microglia regulate astrogliosis by using lipopolysaccharide (LPS) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse PD models...
August 2017: Redox Biology
https://www.readbyqxmd.com/read/28202386/paraquat-and-maneb-co-exposure-induces-noradrenergic-locus-coeruleus-neurodegeneration-through-nadph-oxidase-mediated-microglial-activation
#13
Liyan Hou, Cong Zhang, Ke Wang, Xiaofang Liu, Hongwei Wang, Yuning Che, Fuqiang Sun, Xueying Zhou, Xiulan Zhao, Qingshan Wang
Co-exposure to paraquat (PQ) and maneb (Mb) has been shown to increase the risk of Parkinson's disease (PD) and dopaminergic (DA) neurodegeneration in the substantia nigra pars compacta (SNpc) is observed in PQ and Mb-treated experimental animals. The loss of noradrenergic locus coeruleus (LC/NE) neurons in brainstem is a common feature shared by multiple neurodegenerative diseases, including PD. However, whether PQ and Mb is able to damage LC/NE neurons remains undefined. In this study, mice treated with combined PQ and Mb displayed progressive LC/NE neurodegeneration...
April 1, 2017: Toxicology
https://www.readbyqxmd.com/read/28145852/safranal-prevents-rotenone-induced-oxidative-stress-and-apoptosis-in-an-in-vitro-model-of-parkinson-s-disease-through-regulating-keap1-nrf2-signaling-pathway
#14
P-K Pan, L-Y Qiao, X-N Wen
Safranal, a major constituent of saffron, possesses antioxidant and anti-apoptotic properties showing considerable neuroprotective effects. However, whether safranal shows therapeutic effect on Parkinson's disease (PD) remains unknown. In this study, we aimed to investigate the potential effect of safranal on PD using an in vitro model of PD induced by rotenone. We found that safranal significantly inhibited rotenone-induced cell death in a dose-dependent manner. Moreover, safranal also markedly suppressed the reactive oxygen species (ROS) generation and cell apoptosis induced by rotenone...
December 30, 2016: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28095923/nadph-oxidase-in-brain-injury-and-neurodegenerative-disorders
#15
REVIEW
Merry W Ma, Jing Wang, Quanguang Zhang, Ruimin Wang, Krishnan M Dhandapani, Ratna K Vadlamudi, Darrell W Brann
Oxidative stress is a common denominator in the pathology of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis, as well as in ischemic and traumatic brain injury. The brain is highly vulnerable to oxidative damage due to its high metabolic demand. However, therapies attempting to scavenge free radicals have shown little success. By shifting the focus to inhibit the generation of damaging free radicals, recent studies have identified NADPH oxidase as a major contributor to disease pathology...
January 17, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28042770/preventive-and-protective-roles-of-dietary-nrf2-activators-against-central-nervous-system-diseases
#16
Yang Sun, Tuo Yang, Rehana K Leak, Jun Chen, Feng Zhang
Central nervous system diseases are major health issues and are often associated with disability or death. Most central nervous system disorders are characterized by high levels of oxidative stress. Nuclear factor erythroid 2 related factor (Nrf2) is known for its ability to regulate the expression of a series of enzymes with antioxidative, prosurvival, and detoxification effects. Under basal conditions, Nrf2 forms a complex with Kelch-like ECH associated protein 1, leading to Nrf2 inactivation via ubiquitination and degradation...
2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/27693730/menopause-and-parkinson-s-disease-interaction-between-estrogens-and-brain-renin-angiotensin-system-in-dopaminergic-degeneration
#17
REVIEW
Jose L Labandeira-Garcia, Ana I Rodriguez-Perez, Rita Valenzuela, Maria A Costa-Besada, Maria J Guerra
The neuroprotective effects of menopausal hormonal therapy in Parkinson's disease (PD) have not yet been clarified, and it is controversial whether there is a critical period for neuroprotection. Studies in animal models and clinical and epidemiological studies indicate that estrogens induce dopaminergic neuroprotection. Recent studies suggest that inhibition of the brain renin-angiotensin system (RAS) mediates the effects of estrogens in PD models. In the substantia nigra, ovariectomy induces a decrease in levels of estrogen receptor-α (ER-α) and increases angiotensin activity, NADPH-oxidase activity and expression of neuroinflammatory markers, which are regulated by estrogen replacement therapy...
October 2016: Frontiers in Neuroendocrinology
https://www.readbyqxmd.com/read/27610168/peganum-harmala-l-extract-reduces-oxidative-stress-and-improves-symptoms-in-6-hydroxydopamine-induced-parkinson-s-disease-in-rats
#18
Maryam Rezaei, Sima Nasri, Mehrdad Roughani, Zeinab Niknami, Seyed Ali Ziai
Parkinson's disease is one of the most common neurodegenerative disorders. There are many documents about the effects of oxidative stress in Parkinson's disease etiology. Angiotensin II activates NADPH dependent oxidases and causes superoxides formation. Peganum harmala L. extract, which has angiotensin converting enzyme (ACE) inhibitory effect, is considered to evaluate oxidative stress inhibition and Parkinson's disease improvement. Male rats weighting 200-250 g were divided into 5 groups: Control, Neurotoxin (injection of 6-hydroxydopamine into left hemisphere substantia nigra), Peganum harmala's seeds aqueous extract (10 mg/kg) and captopril (5 mg/kg)...
2016: Iranian Journal of Pharmaceutical Research: IJPR
https://www.readbyqxmd.com/read/27477685/redox-based-therapeutics-in-neurodegenerative-disease
#19
REVIEW
G J McBean, M G López, F K Wallner
This review describes recent developments in the search for effective therapeutic agents that target redox homeostasis in neurodegenerative disease. The disruption to thiol redox homeostasis in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and multiple sclerosis is discussed, together with the experimental strategies that are aimed at preventing, or at least minimizing, oxidative damage in these diseases. Particular attention is given to the potential of increasing antioxidant capacity by targeting the Nrf2 pathway, the development of inhibitors of NADPH oxidases that are likely candidates for clinical use, together with strategies to reduce nitrosative stress and mitochondrial dysfunction...
June 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27329107/identification-of-a-specific-%C3%AE-synuclein-peptide-%C3%AE-syn-29-40-capable-of-eliciting-microglial-superoxide-production-to-damage-dopaminergic-neurons
#20
Shijun Wang, Chun-Hsien Chu, Mingri Guo, Lulu Jiang, Hui Nie, Wei Zhang, Belinda Wilson, Li Yang, Tessandra Stewart, Jau-Shyong Hong, Jing Zhang
BACKGROUND: Misfolded α-synuclein (α-Syn) aggregates participate in the pathogenesis of synucleinopathies, such as Parkinson's disease. Whereas much is known about how the various domains within full-length α-Syn (FL-α-Syn) contribute to the formation of α-Syn aggregates and therefore to their neurotoxicity, little is known about whether the individual peptides that can be generated from α-syn, possibly as intermediate metabolites during degradation of misfolded α-Syn aggregates, are neurotoxic themselves...
June 21, 2016: Journal of Neuroinflammation
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