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Oxidative stress AND multiple sclerosis

Ruihe Lin, Jingli Cai, Eric W Kostuk, Robert Rosenwasser, Lorraine Iacovitti
BACKGROUND: Dimethyl fumarate (DMF), working via its metabolite monomethylfumarate (MMF), acts as a potent antioxidant and immunomodulator in animal models of neurologic disease and in patients with multiple sclerosis. These properties and their translational potential led us to investigate whether DMF/MMF could also protect at-risk and/or dying neurons in models of ischemic stroke in vitro and in vivo. Although the antioxidant effects have been partially addressed, the benefits of DMF immunomodulation after ischemic stroke still need to be explored...
October 13, 2016: Journal of Neuroinflammation
Shohei Murakami, Hozumi Motohashi
The KEAP1-NRF2 system is an inducible molecular mechanism enhancing transcriptions of several cytoprotective genes in response to xenobiotics and oxidative stress. Recently, the KEAP1-NRF2 system has been suggested to directly regulate a portion of the genes related to cell proliferation and differentiation. In hematopoietic cells, NRF2 activation plays a role in maintenance and cell fate determination of hematopoietic stem cells, as well as in maturation processes and homeostasis of megakaryocytes and erythrocytes...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Rachel Waller, M Nicola Woodroofe, Stephen B Wharton, Paul G Ince, Simona Francese, Paul R Heath, Alex Cudzich-Madry, Ruth H Thomas, Natalie Rounding, Basil Sharrack, Julie E Simpson
Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS). White matter lesions in MS are surrounded by areas of non-demyelinated normal appearing white matter (NAWM) with complex pathology, including blood brain barrier dysfunction, axonal damage and glial activation. Astrocytes, the most abundant cell type within the CNS, may respond and/or contribute to lesion pathogenesis. We aimed to characterise the transcriptomic profile of astrocytes in NAWM to determine whether specific glial changes exist in the NAWM which contribute to lesion development or prevent disease progression...
October 15, 2016: Journal of Neuroimmunology
Begoña M Escribano, Francisco J Medina-Fernández, Macarena Aguilar-Luque, Eduardo Agüera, Montserrat Feijoo, Fe I Garcia-Maceira, Rafael Lillo, Patricia Vieyra-Reyes, Ana I Giraldo, Evelio Luque, René Drucker-Colín, Isaac Túnez
Recent findings in experimental autoimmune encephalomyelitis (EAE) suggest that altering certain bacterial populations present in the gut may lead to a proinflammatory condition, that could result in the development of multiple sclerosis (MS). Also, Reactive Oxygen Species seem to be involved in the course of MS. In this study, it has been aimed to relate all these variables starting from an analysis of the lipopolysaccharide (LPS) and LPS-binding protein (LBP) with the determination of parameters related to oxidative stress in the blood, brain and spinal cord...
October 7, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Katharine E Stahon, Chinthasagar Bastian, Shelby Griffith, Grahame J Kidd, Sylvain Brunet, Selva Baltan
UNLABELLED: The impact of aging on CNS white matter (WM) is of general interest because the global effects of aging on myelinated nerve fibers are more complex and profound than those in cortical gray matter. It is important to distinguish between axonal changes created by normal aging and those caused by neurodegenerative diseases, including multiple sclerosis, stroke, glaucoma, Alzheimer's disease, and traumatic brain injury. Using three-dimensional electron microscopy, we show that in mouse optic nerve, which is a pure and fully myelinated WM tract, aging axons are larger, have thicker myelin, and are characterized by longer and thicker mitochondria, which are associated with altered levels of mitochondrial shaping proteins...
September 28, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Ebrahim Kouchaki, Omid Reza Tamtaji, Mahmoud Salami, Fereshteh Bahmani, Reza Daneshvar Kakhaki, Elmira Akbari, Maryam Tajabadi-Ebrahimi, Parvaneh Jafari, Zatollah Asemi
BACKGROUND & AIMS: This trial was performed to evaluate the effects of probiotic intake on disability, mental health and metabolic condition in subjects with multiple sclerosis (MS). METHODS: This randomized double-blind placebo-controlled clinical trial was conducted among 60 MS patients. Participants were randomly allocated into two groups to receive either a probiotic capsule (n = 30) or placebo containing starch (n = 30) for 12 weeks. Expanded disability status scale (EDSS) scoring and parameters of mental health were recorded at the baseline and 12 weeks after the intervention...
September 16, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
T Draheim, A Liessem, M Scheld, F Wilms, M Weißflog, B Denecke, T W Kensler, A Zendedel, C Beyer, M Kipp, C J Wruck, A Fragoulis, T Clarner
Oxidative stress critically contributes to the pathogenesis of a variety of neurodegenerative diseases such as multiple sclerosis. Astrocytes are the main regulators of oxidative homeostasis in the brain and dysregulation of these cells likely contributes to the accumulation of oxidative damage. The nuclear factor erythroid 2-related factor 2 (Nrf2) is the main transcriptional regulator of the anti-oxidant stress defense. In this study, we elucidate the effects of astrocytic Nrf2-activation on brain-intrinsic inflammation and lesion development...
September 19, 2016: Glia
Moses Rodriguez, Bharath Wootla, George Anderson
BACKGROUND: Alterations in gut microbiota, coupled to increased gut permeability are now widely recognized as having a role in the etiology, course and treatment of many medical conditions, including autoimmune and neurodegenerative disorders. METHODS: In this review, the role that such gut changes play over the course of multiple sclerosis (MS) is detailed. RESULTS: Given the wide array of biological factors and processes that have been shown to be altered in MS, including changes in the gut, this allows for a better integration of the diverse array of pathophysiological processes linked to MS...
September 15, 2016: Current Pharmaceutical Design
In-Young Choi, Phil Lee, Abbey J Hughes, Douglas R Denney, Sharon G Lynch
BACKGROUND: Increased oxidative stress leads to loss of glutathione (GSH). We have reported lower cerebral GSH in patients with secondary progressive multiple sclerosis (SPMS), indicating the involvement of oxidative stress in multiple sclerosis (MS) pathophysiology. OBJECTIVE: This study expanded upon our earlier work by examining longitudinal changes in cerebral GSH in patients with SPMS in relation to their clinical status. METHODS: A total of 13 patients with SPMS (Expanded Disability Status Scale (EDSS) = 4...
September 12, 2016: Multiple Sclerosis: Clinical and Laboratory Research
Jamie L Lim, Susanne M A van der Pol, Wia Baron, Joe M McCord, Helga E de Vries, Jack van Horssen
Oligodendrocyte damage and loss are key features of multiple sclerosis (MS) pathology. Oligodendrocytes appear to be particularly vulnerable to reactive oxygen species (ROS) and cytokines, such as tumor necrosis factor-α (TNF), which induce cell death and prevent the differentiation of oligodendrocyte progenitor cells (OPCs). Here, we investigated the efficacy of sulforaphane (SFN), monomethyl fumarate (MMF) and Protandim to induce Nrf2-regulated antioxidant enzyme expression, and protect oligodendrocytes against ROS-induced cell death and ROS-and TNF-mediated inhibition of OPC differentiation...
September 7, 2016: Antioxidants (Basel, Switzerland)
Sandra Guidi, Patrizia Bianchi, Fiorenza Stagni, Andrea Giacomini, Marco Emili, Stefania Trazzi, Elisabetta Ciani, Renata Bartesaghi
In this review we look at this biological overlaps of neurodegenerative and psychiatric conditions, as exemplified by major depressive disorder (MDD). Recent work has highlighted how immune-inflammatory processes and their interactions with oxidative and nitrosative stress (O&NS), couple to drive changes in neuroregulatory tryptophan catabolite (TRYCAT), with consequences for serotonin availability for the melatonergic pathways. Such work significantly questions the validity and utility of non-biologically based current classification systems for psychiatric and neurodegenerative conditions...
August 1, 2016: CNS & Neurological Disorders Drug Targets
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
Priscila S Souza, Elaine D Gonçalves, Giulia S Pedroso, Hemelin R Farias, Stella C Junqueira, Rodrigo Marcon, Talita Tuon, Maíra Cola, Paulo C L Silveira, Adair R Santos, João B Calixto, Cláudio T Souza, Ricardo A de Pinho, Rafael C Dutra
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) caused by demyelination, immune cell infiltration, and axonal damage. Herein, we sought to investigate the influence of physical exercise on mice experimental autoimmune encephalomyelitis (EAE), a reported MS model. Data show that both strength and endurance training protocols consistently prevented clinical signs of EAE and decreased oxidative stress, an effect which was likely due to improving genomic antioxidant defense-nuclear factor erythroid 2-related factor (Nrf2)/antioxidant response elements (ARE) pathway-in the CNS...
July 22, 2016: Molecular Neurobiology
Shinji Hadano, Shun Mitsui, Lei Pan, Asako Otomo, Mizuki Kubo, Kai Sato, Suzuka Ono, Wakana Onodera, Koichiro Abe, XuePing Chen, Masato Koike, Yasuo Uchiyama, Masashi Aoki, Eiji Warabi, Masayuki Yamamoto, Tetsuro Ishii, Toru Yanagawa, Hui-Fang Shang, Fumihito Yoshii
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by a selective loss of motor neurons in the brain and spinal cord. Multiple toxicity pathways, such as oxidative stress, misfolded protein accumulation, and dysfunctional autophagy, are implicated in the pathogenesis of ALS. However, molecular basis of the interplay between such multiple factors in vivo remains unclear. Here, we report that two independent ALS-linked autophagy-associated gene products; SQSTM1/p62 and ALS2/alsin, but not antioxidant-related factor; NFE2L2/Nrf2, are implicated in the pathogenesis in mutant SOD1 transgenic ALS models...
July 20, 2016: Human Molecular Genetics
Richard Ibitoye, Kevin Kemp, Claire Rice, Kelly Hares, Neil Scolding, Alastair Wilkins
AIM: To provide an up-to-date review of oxidative stress biomarkers in multiple sclerosis and thus identify candidate molecules with greatest promise as biomarkers of diagnosis, disease activity or prognosis. METHOD: A semi-systematic literature search using PubMed and other databases. RESULTS: Nitric oxide metabolites, superoxide dismutase, catalase, glutathione reductase, inducible nitric oxide synthase, protein carbonyl, 3-nitrotyrosine, isoprostanes, malondialdehyde and products of DNA oxidation have been identified across multiple studies as having promise as diagnostic, therapeutic or prognostic markers in MS...
August 2016: Biomarkers in Medicine
M A Greenough, A Ramírez Munoz, A I Bush, C M Opazo
Copper is an essential metal ion that provides catalytic function to numerous enzymes and also regulates neurotransmission and intracellular signaling. Conversely, a deficiency or excess of copper can cause chronic disease in humans. Menkes and Wilson disease are two rare heritable disorders of copper transport that are characterized by copper deficiency and copper overload, respectively. Changes to copper status are also a common feature of several neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS)...
September 1, 2016: Metallomics: Integrated Biometal Science
Magda A Lam, Ghassan J Maghzal, Mohsen Khademi, Fredik Piehl, Rikke Ratzer, Jeppe Romme Christensen, Finn Thorup Sellebjerg, Tomas Olsson, Roland Stocker
OBJECTIVE: We aimed to investigate the role of oxidative stress in the progression of multiple sclerosis (MS). METHODS: We determined by liquid chromatography-tandem mass spectrometry nonenzymatic (F2-isoprostanes) and enzymatic oxidation products of arachidonic acid (prostaglandin F2α [PGF2α]) in plasma and CSF of 45 controls (other neurologic disease [OND] with no signs of inflammation) and 62 patients with MS. Oxidation products were correlated with disease severity and validated biomarkers of inflammation (chemokine ligand 13; matrix metalloproteinase-9; osteopontin) and axonal damage (neurofilament light protein)...
August 2016: Neurology® Neuroimmunology & Neuroinflammation
Thomas Müller, Thomas Herrling, Sven Lütge, Lutz Lohse, Gabi Öhm, Katinka Jung
INTRODUCTION: Cerebrospinal fluid analysis may provide insight into the interplay between chronic inflammation and response to treatment. OBJECTIVES: To demonstrate the impact of one intrathecal triamcinolone injection on the redox potential and on ascorbyl radical appearance in the cerebrospinal fluid of chronic progressive multiple sclerosis patients. METHODS: A total of 16 patients received 40 mg triamcinolone. Electron-spin resonance spectroscopy measured the oxidation range after copper ion [Cu (II)] addition and ascorbyl-radical bioavailability...
July 2016: Therapeutic Advances in Neurological Disorders
Marco Fiore, Mauro Ceccanti, Valentina Carito, Luigi Tarani, Giampiero Ferraguti, George N Chaldakov
: Polyphenols are probably the most known and investigated molecules of nutritional interest as micronutrients present in abundance in our diet. Some of the most important food sources of polyphenols in the Mediterranean diet are olives and olive oil. A growing body of evidence from animal models to clinical studies indicates that polyphenol compounds may have neuroprotective effects in several pathologies of the nervous system through the control of oxidative stress, inflammation, apoptosis and mitochondrial dysfunction...
June 26, 2016: Current Medicinal Chemistry
R S Ray, Anju Katyal
Neurodegenerative conditions present a group of complex disease pathologies mostly due to unknown aetiology resulting in neuronal death and permanent neurological disability. Any undesirable stress to the brain, disrupts homeostatic balance, through a remarkable convergence of pathophysiological changes and immune dysregulation. The crosstalk between inflammatory and oxidative mechanisms results in the release of neurotoxic mediators apparently spearheaded by myeloperoxidase derived from activated microglia, astrocytes, neurons as well as peripheral inflammatory cells...
September 2016: Neuroscience and Biobehavioral Reviews
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