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NadPH AND Parkinsons

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
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
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
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...
February 22, 2017: Redox Biology
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...
February 13, 2017: Toxicology
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
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
Yang Sun, Tuo Yang, Rehana K Leak, Jun-He 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...
January 2, 2017: CNS & Neurological Disorders Drug Targets
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
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
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 minimising, 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 usage, together with strategies to reduce nitrosative stress and mitochondrial dysfunction...
August 1, 2016: British Journal of Pharmacology
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...
2016: Journal of Neuroinflammation
Lulu Jiang, Xuefei Wu, Shuo Wang, Shih-Heng Chen, Hui Zhou, Belinda Wilson, Chun-Yang Jin, Ru-Band Lu, Keqin Xie, Qingshan Wang, Jau-Shyong Hong
BACKGROUND: Clozapine, an atypical antipsychotic medication, has been effectively used to treat refractory schizophrenia. However, the clinical usage of clozapine is limited due to a high incidence of neutropenia or agranulocytosis. We previously reported that clozapine protected dopaminergic neurons through inhibition of microglial activation. The purpose of this study was to explore the neuroprotective effects of clozapine metabolites clozapine N-oxide (CNO) and N-desmethylclozapine (NDC), as well as their propensity to cause neutropenia...
2016: Journal of Neuroinflammation
Zhaoyang Hu, Wei Wang, Jing Ling, Chunming Jiang
Microglia-mediated neuroinflammation induced by α-synuclein in the substantianigra likely either initiates or aggravates nigral neuro degeneration in Parkinson's disease (PD). We aimed to explore the effects of α-mangostin (α-M), a polyphenolicxanthone derivative from mangosteen on α-synuclein-stimulated DA neurodegeneration. Primary microglia, mesencephalic neuron, mesencephalic neuron-glianeuronal cultures, and transwell co-cultures were prepared separately. Liquid scintillation counting was used to determine the radioactivity in DA uptake...
July 2016: Cellular and Molecular Neurobiology
Rituraj Pal, Lakshya Bajaj, Jaiprakash Sharma, Michela Palmieri, Alberto Di Ronza, Parisa Lotfi, Arindam Chaudhury, Joel Neilson, Marco Sardiello, George G Rodney
Oxidative stress and aberrant accumulation of misfolded proteins in the cytosol are key pathological features associated with Parkinson's disease (PD). NADPH oxidase (Nox2) is upregulated in the pathogenesis of PD; however, the underlying mechanism(s) of Nox2-mediated oxidative stress in PD pathogenesis are still unknown. Using a rotenone-inducible cellular model of PD, we observed that a short exposure to rotenone (0.5 μM) resulted in impaired autophagic flux through activation of a Nox2 dependent Src/PI3K/Akt axis, with a consequent disruption of a Beclin1-VPS34 interaction that was independent of mTORC1 activity...
2016: Scientific Reports
Dan Ploug Christensen, Patrick Ejlerskov, Izabela Rasmussen, Frederik Vilhardt
BACKGROUND: Secretion of proteopathic α-synuclein (α-SNC) species from neurons is a suspected driving force in the propagation of Parkinson's disease (PD). We have previously implicated exophagy, the exocytosis of autophagosomes, as a dominant mechanism of α-SNC secretion in differentiated PC12 or SH-SY5Y nerve cells. Here we have examined the regulation of exophagy associated with different forms of nerve cell stress relevant to PD. RESULTS: We identify cJUN-N-terminal kinase (JNK) activity as pivotal in the secretory fate of autophagosomes containing α-SNC...
March 8, 2016: Journal of Neuroinflammation
Wei-Ting Tseng, Ya-Wen Hsu, Tzu-Ming Pan
Context Oxidative stress plays a key role in neurodegenerative disorders, including Parkinson's disease (PD). Rice fermented with Monascus purpureus Went (Monascaceae) NTU 568 (red mould rice) was found to contain antioxidants, including dimerumic acid (DMA) and deferricoprogen (DFC). Objective The effects of DMA and DFC on 6-hydroxydopamine (6-OHDA)-induced cytotoxicity and potential protective mechanisms in differentiated PC-12 pheochromocytoma cells were investigated. Materials and methods DMA (0-60 μM) or DFC (0-10 μM) was co-treated with 6-OHDA (200 μM, 24 h exposure) in differentiated PC-12 cells...
August 2016: Pharmaceutical Biology
Jun Wang, Can He, Wang-Yang Wu, Feng Chen, Yang-Yang Wu, Wei-Zu Li, Han-Qing Chen, Yan-Yan Yin
Parkinson's disease (PD) is the second most common neurodegenerative disease, which is characterized by loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Accumulated evidences have suggested that oxidative stress is closely associated with the dopaminergic neurodegeneration of PD that can be protected by antioxidants. Biochanin A that is an O-methylated isoflavone in chickpea is investigated to explore its protective mechanism on dopaminergic neurons of the unilateral lipopolysaccharide (LPS)-injected rat...
November 2015: Pharmacology, Biochemistry, and Behavior
Kondalarao Bankapalli, SreeDivya Saladi, Sahezeel S Awadia, Arvind Vittal Goswami, Madhuja Samaddar, Patrick D'Silva
Methylglyoxal (MG) is a reactive metabolic intermediate generated during various cellular biochemical reactions, including glycolysis. The accumulation of MG indiscriminately modifies proteins, including important cellular antioxidant machinery, leading to severe oxidative stress, which is implicated in multiple neurodegenerative disorders, aging, and cardiac disorders. Although cells possess efficient glyoxalase systems for detoxification, their functions are largely dependent on the glutathione cofactor, the availability of which is self-limiting under oxidative stress...
October 30, 2015: Journal of Biological Chemistry
Neha Sharma, Monika Kapoor, Bimla Nehru
Parkinson's disease (PD), is an age-related, progressive neurodegenerative disorder that affects movement and is characterized by the loss of dopaminergic neurons in the nigrostriatal region. Although the clinical and pathological features of PD are complex, recent studies have indicated that microglial NADPH oxidase play a key role in its pathology. A little information is available regarding the role of apocyanin, an NADPH oxidase inhibitor, in ameliorating α-synuclein aggregation and neurobehavioral consequences of PD...
January 1, 2016: Behavioural Brain Research
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