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Stress model for neurodegenerative disorders

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https://www.readbyqxmd.com/read/28894122/onset-of-disorder-and-protein-aggregation-due-to-oxidation-induced-intermolecular-disulfide-bonds-case-study-of-rrm2-domain-from-tdp-43
#1
Sevastyan O Rabdano, Sergei A Izmailov, Dmitrii A Luzik, Adam Groves, Ivan S Podkorytov, Nikolai R Skrynnikov
We have investigated the behavior of second RNA-recognition motif (RRM2) of neuropathological protein TDP43 under the effect of oxidative stress as modeled in vitro. Toward this end we have used the specially adapted version of H/D exchange experiment, NMR relaxation and diffusion measurements, dynamic light scattering, controlled proteolysis, gel electrophoresis, site-directed mutagenesis and microsecond MD simulations. Under oxidizing conditions RRM2 forms disulfide-bonded dimers that experience unfolding and then assemble into aggregate particles (APs)...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28865316/oxidative-species-induced-excitonic-transport-in-tubulin-aromatic-networks-potential-implications-for-neurodegenerative-disease
#2
P Kurian, T O Obisesan, T J A Craddock
Oxidative stress is a pathological hallmark of neurodegenerative tauopathic disorders such as Alzheimer's disease and Parkinson's disease-related dementia, which are characterized by altered forms of the microtubule-associated protein (MAP) tau. MAP tau is a key protein in stabilizing the microtubule architecture that regulates neuron morphology and synaptic strength. When MAP tau is degraded in tauopathic disorders, neuron dysfunction results. The precise role of reactive oxygen species (ROS) in the tauopathic disease process, however, is poorly understood...
August 24, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28840449/from-mitochondrial-function-to-neuroprotection-an-emerging-role-for-methylene-blue
#3
REVIEW
Donovan Tucker, Yujiao Lu, Quanguang Zhang
Methylene blue (MB) is a well-established drug with a long history of use, owing to its diverse range of use and its minimal side effect profile. MB has been used classically for the treatment of malaria, methemoglobinemia, and carbon monoxide poisoning, as well as a histological dye. Its role in the mitochondria, however, has elicited much of its renewed interest in recent years. MB can reroute electrons in the mitochondrial electron transfer chain directly from NADH to cytochrome c, increasing the activity of complex IV and effectively promoting mitochondrial activity while mitigating oxidative stress...
August 24, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28837626/trehalose-improves-traumatic-brain-injury-induced-cognitive-impairment
#4
Stuart D Portbury, Dominic J Hare, David I Finkelstein, Paul A Adlard
Traumatic brain Injury (TBI) is a significant cause of death and long-term disability for which there are currently no effective pharmacological treatment options. In this study then, we utilized a mouse model of TBI to assess the therapeutic potential of the stable disaccharide trehalose, which is known to protect against oxidative stress, increase levels of chaperone molecules and enhance autophagy. Furthermore, trehalose has demonstrated neuroprotective properties in numerous animal models and has been proposed as a potential treatment for neurodegeneration...
2017: PloS One
https://www.readbyqxmd.com/read/28837568/progranulin-gene-delivery-reduces-plaque-burden-and-synaptic-atrophy-in-a-mouse-model-of-alzheimer-s-disease
#5
Jackalina M Van Kampen, Denis G Kay
Progranulin (PGRN) is a multifunctional protein that is widely expressed throughout the brain, where it has been shown to act as a critical regulator of CNS inflammation and also functions as an autocrine neuronal growth factor, important for long-term neuronal survival. PGRN has been shown to activate cell signaling pathways regulating excitoxicity, oxidative stress, and synaptogenesis, as well as amyloidogenesis. Together, these critical roles in the CNS suggest that PGRN has the potential to be an important therapeutic target for the treatment of various neurodegenerative disorders, particularly Alzheimer's disease (AD)...
2017: PloS One
https://www.readbyqxmd.com/read/28830914/n-acetyl-l-cysteine-protects-astrocytes-against-proteotoxicity-without-recourse-to-glutathione
#6
Amanda M Gleixner, Daniel F Hutchison, Sara Sannino, Tarun N Bhatia, Lillian C Leak, Patrick T Flaherty, Peter Wipf, Jeffrey L Brodsky, Rehana K Leak
N-Acetyl-L-cysteine (NAC) exhibits protective properties in brain injury models and has undergone a number of clinical trials. Most studies of NAC have focused on neurons. However, neuroprotection may be complemented by the protection of astrocytes because healthier astrocytes can better support the viability of neurons. Here we show that NAC can protect astrocytes against protein misfolding stress (proteotoxicity), the hallmark of neurodegenerative disorders. Although NAC is thought to be a glutathione precursor, NAC protected primary astrocytes from the toxicity of the proteasome inhibitor MG132 without eliciting any increase in glutathione...
August 22, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28819888/paraquat-induced-movement-disorder-in-relation-to-oxidative-stress-mediated-neurodegeneration-in-the-brain-of-drosophila-melanogaster
#7
S Niveditha, S R Ramesh, T Shivanandappa
Exposure to pesticides like paraquat (PQ) is considered as a risk factor for Parkinson's disease (PD). PQ has been shown to induce PD-like phenotype in experimental animals. Drosophila, a valuable laboratory model organism, is widely used to study neurodegenerative disorders including PD. The acute (single dose) PQ model of PD in Drosophila is associated with high mortality as well as reversibility of locomotor deficits and, therefore, does not replicate the disease phenotype. We have investigated the relevance of the acute and multiple (sublethal) dose of PQ to induce PD-like symptoms in Drosophila and shown that multiple-dose of PQ induces irreversible locomotor impairment without significant mortality...
August 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28813475/evaluation-of-the-adaptogenic-potential-exerted-by-ginsenosides-rb1-and-rg1-against-oxidative-stress-mediated-neurotoxicity-in-an-in-vitro-neuronal-model
#8
Carlos Fernández-Moriano, Elena González-Burgos, Irene Iglesias, Rafael Lozano, M Pilar Gómez-Serranillos
BACKGROUND: Ginseng (Panax sp.) is a drug with multiple pharmacological actions that has been largely used in traditional medicines for the treatment of many health problems. In the therapy of neurodegenerative disorders, it has been employed due to its capacity to strengthen mental processes by enhancing cognitive performance and psychological function. Current work aimed at evaluating the adaptogenic potential of Rb1 and Rg1 against oxidative-stress mediated degeneration in a model of nervous cells...
2017: PloS One
https://www.readbyqxmd.com/read/28812474/protective-effect-of-raisin-currant-against-spatial-memory-impairment-and-oxidative-stress-in-alzheimer-disease-model
#9
Mohammad Gol, Davoud Ghorbanian, Nabiollah Soltanpour, Jamshid Faraji, Mohsen Pourghasem
OBJECTIVES: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive pathological changes of the brain. A number of studies demonstrated compelling evidence of the importance of oxidative processes in AD pathogenesis. Raisin contains polyphenol, phenolic acid, and tannin compounds, which have antioxidant and anti-inflammatory properties. The present study was aimed to evaluate the protective effect of raisin on neurobehavioral and histological changes in rats with Alzheimer...
August 16, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28810923/the-chemokine-fractalkine-cx3cl1-attenuates-h2o2-induced-demyelination-in-cerebellar-slices
#10
Sinead A O'Sullivan, Kumlesh K Dev
BACKGROUND: Fractalkine/CX3CR1 signalling has been implicated in many neurodegenerative and neurological diseases of the central nervous system (CNS). This signalling pathway plays an important role in regulating reactive oxygen species (ROS), as well as itself being altered in conditions of oxidative stress. Here, we investigated the effects of recombinant fractalkine (rCX3CL1) in models of hydrogen peroxide (H2O2)-induced demyelination and astrocyte toxicity, within organotypic cerebellar slice cultures...
August 15, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28797292/the-ethanol-extract-of-aquilariae-lignum-ameliorates-hippocampal-oxidative-stress-in-a-repeated-restraint-stress-mouse-model
#11
Hyun-Yong Lee, Jin-Seok Lee, Hyeong-Geug Kim, Won-Yong Kim, Seung-Bae Lee, Yung-Hyun Choi, Chang-Gue Son
BACKGROUND: Chronic stress contributes to the development of brain disorders, such as neurodegenerative and psychiatric diseases. Oxidative damage is well known as a causative factor for pathogenic process in brain tissues. The aim of this study is to evaluate the neuroprotective effect of a 30% ethanol extract of Aquilariae Lignum (ALE) in repeated stress-induced hippocampal oxidative injury. METHODS: Fifty BALB/c male mice (12 weeks old) were randomly divided into five groups (n = 10)...
August 10, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28774789/impaired-cbs-h2s-signaling-axis-contributes-to-mptp-induced-neurodegeneration-in-a-mouse-model-of-parkinson-s-disease
#12
Yu-Qing Yuan, Ya-Li Wang, Bao-Shi Yuan, Xin Yuan, Xiao-Ou Hou, Jin-Song Bian, Chun-Feng Liu, Li-Fang Hu
Hydrogen sulfide (H2S), a novel neuromodulator, is linked to the pathogenesis of several neurodegenerative disorders. Exogenous application of H2S exerts neuroprotection via anti-inflammation and anti-oxidative stress in animal and cellular models of Parkinson's disease (PD). However, the role of endogenous H2S and the contribution of its various synthases in PD remain unclear. In the present study, we found a decline of plasma and striatal sulfide level in 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced PD mouse model...
August 1, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28764908/neuroprotective-effects-of-lentivirus-mediated-cystathionine-beta-synthase-overexpression-against-6-ohda-induced-parkinson-s-disease-rats
#13
Yin Weilan, Yin Weiguo, Huang Baisheng, Wu Lixiang
Parkinson's disease (PD) is age-related neurodegenerative disorder by a progressive loss of dopaminergic(DA) neurons in the substantia nigra (SN) and striatum, which is at least partly associated with α-synuclein protein accumulation in these neurons. Hydrogen sulfide (H2S) plays an important role in the nervous system. Studies have shown that H2S has a protective effect on PD. However, as a kind of gas molecules, H2S is lively, volatile, and not conducive to scientific research and clinical application. Cystathionine-beta-synthase(CBS) is the main enzymes of synthesis of H2S in the brain...
July 29, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28750802/modeling-neurodegenerative-disorders-for-developing-cannabinoid-based-neuroprotective-therapies
#14
Javier Fernández-Ruiz, María Gómez-Ruiz, Concepción García, Mariluz Hernández, José A Ramos
The increase in lifespan during the last 50 years, mainly in developed countries, has originated a progressive elevation in the incidence of chronic neurodegenerative disorders, for which aging is the key risk factor. This fact will definitively become the major biomedical challenge during the present century, in part because the expectation of a persisting elevation in the population older than 65 years over the whole population and, on the other hand, because the current lack of efficacious therapies to control these disorders despite years of intense research...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28721811/moving-to-the-rhythm-with-clock-circadian-genes-autophagy-mtor-and-sirt1-in-degenerative-disease-and-cancer
#15
Kenneth Maiese
BACKGROUND: The mammalian circadian clock and its associated clock genes are increasingly been recognized as critical components for a number of physiological and disease processes that extend beyond hormone release, thermal regulation, and sleep-wake cycles. New evidence suggests that clinical behavior disruptions that involve prolonged shift work and even space travel may negatively impact circadian rhythm and lead to multi-system disease. METHODS: In light of the significant role circadian rhythm can hold over the body's normal physiology as well as disease processes, we examined and discussed the impact circadian rhythm and clock genes hold over lifespan, neurodegenerative disorders, and tumorigenesis...
2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/28717189/cdk5-mediated-phosphorylation-of-xbp1s-contributes-to-its-nuclear-translocation-and-activation-in-mpp-induced-parkinson-s-disease-model
#16
Feng-Juan Jiao, Qing-Zhi Wang, Pei Zhang, Jian-Guo Yan, Zheng Zhang, Feng He, Qian Zhang, Ze-Xi Lv, Xiang Peng, Hong-Wei Cai, Bo Tian
Parkinson's disease (PD) is an irreversible and progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons of the substantia nigra pars compacta. Growing evidence indicates that endoplasmic reticulum stress is a hallmark of PD; however, its exact contribution to the disease process remains poorly understood. Here, we used molecular biology methods and RNA-Seq analysis to explored an unexpected role of spliced X-Box binding protein 1 (XBP1s) in the nervous system. In this study, we determined that the IRE1α/XBP1 pathway is activated in MPP(+)-treated neurons...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28684694/neuroprotective-effects-of-%C3%AE-caryophyllene-against-dopaminergic-neuron-injury-in-a-murine-model-of-parkinson-s-disease-induced-by-mptp
#17
Juan M Viveros-Paredes, Rocio E González-Castañeda, Juerg Gertsch, Veronica Chaparro-Huerta, Rocio I López-Roa, Eduardo Vázquez-Valls, Carlos Beas-Zarate, Antoni Camins-Espuny, Mario E Flores-Soto
Parkinson's disease (PD) is one of the most common neurodegenerative disorders and is characterized by the loss of dopaminergic neurons in the substantia nigra (SN). Although the causes of PD are not understood, evidence suggests that its pathogenesis is associated with oxidative stress and inflammation. Recent studies have suggested a protective role of the cannabinoid signalling system in PD. β-caryophyllene (BCP) is a natural bicyclic sesquiterpene that is an agonist of the cannabinoid type 2 receptor (CB2R)...
July 6, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28674941/coffee-extract-and-caffeine-enhance-the-heat-shock-response-and-promote-proteostasis-in-an-hsf-1-dependent-manner-in-caenorhabditis-elegans
#18
Jessica Brunquell, Stephanie Morris, Alana Snyder, Sandy D Westerheide
As the population ages, there is a critical need to uncover strategies to combat diseases of aging. Studies in the soil-dwelling nematode Caenorhabditis elegans have demonstrated the protective effects of coffee extract and caffeine in promoting the induction of conserved longevity pathways including the insulin-like signaling pathway and the oxidative stress response. We were interested in determining the effects of coffee and caffeine treatment on the regulation of the heat shock response. The heat shock response is a highly conserved cellular response that functions as a cytoprotective mechanism during stress, mediated by the heat shock transcription factor HSF-1...
July 4, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28673739/sirtuin-3-rescues-neurons-through-the-stabilisation-of-mitochondrial-biogenetics-in-the-virally-expressing-mutant-%C3%AE-synuclein-rat-model-of-parkinsonism
#19
Jacqueline A Gleave, Lindsay R Arathoon, Dennison Trinh, Kristin E Lizal, Nicolas Giguère, James H M Barber, Zainab Najarali, M Hassan Khan, Sherri L Thiele, Mahin S Semmen, James B Koprich, Jonathan M Brotchie, James H Eubanks, Louis-Eric Trudeau, Joanne E Nash
Parkinson's disease (PD) is a neurodegenerative movement disorder, which affects approximately 1-2% of the population over 60years of age. Current treatments for PD are symptomatic, and the pathology of the disease continues to progresses over time until palliative care is required. Mitochondria are key players in the pathology of PD. Genetic and post mortem studies have shown a large number of mitochondrial abnormalities in the substantia nigra pars compacta (SNc) of the parkinsonian brain. Furthermore, physiologically, mitochondria of nigral neurons are constantly under unusually high levels of metabolic stress because of the excitatory properties and architecture of these neurons...
July 1, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28651456/phytochemical-treatments-target-kynurenine-pathway-induced-oxidative-stress
#20
K Parasram
OBJECTIVE: The objective of this paper was to link the phytochemical and metabolic research treating quinolinic acid induced oxidative stress in neurodegenerative disorders. METHODS: Quinolinic acid, a metabolite of the kynurenine pathway of tryptophan catabolism, plays a role in the oxidative stress associated with many neurological disorders and is used to simulate disorders such as Parkinson's disease. RESULTS: In these models, phytochemicals have been shown to reduce striatal lesion size, reduce inflammation and prevent lipid peroxidation caused by quinolinic acid...
June 26, 2017: Redox Report: Communications in Free Radical Research
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