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Oxidative stress AND multiple sclerosis

Jessica M de Souza, Bruno D C Goncalves, Marcus V Gomez, Luciene B Vieira, Fabiola M Ribeiro
Neurodegenerative diseases affect millions of individuals worldwide. So far, no disease-modifying drug is available to treat patients, making the search for effective drugs an urgent need. Neurodegeneration is triggered by the activation of several cellular processes, including oxidative stress, mitochondrial impairment, neuroinflammation, aging, aggregate formation, glutamatergic excitotoxicity, and apoptosis. Therefore, many research groups aim to identify drugs that may inhibit one or more of these events leading to neuronal cell death...
2018: Frontiers in Pharmacology
Michael Dietrich, Niklas Helling, Alexander Hilla, Annemarie Heskamp, Andrea Issberner, Thomas Hildebrandt, Zippora Kohne, Patrick Küry, Carsten Berndt, Orhan Aktas, Dietmar Fischer, Hans-Peter Hartung, Philipp Albrecht
BACKGROUND: In multiple sclerosis (MS), neurodegeneration is the main reason for chronic disability. Alpha-lipoic acid (LA) is a naturally occurring antioxidant which has recently been demonstrated to reduce the rate of brain atrophy in progressive MS. However, it remains uncertain if it is also beneficial in the early, more inflammatory-driven phases. As clinical studies are costly and time consuming, optic neuritis (ON) is often used for investigating neuroprotective or regenerative therapeutics...
March 7, 2018: Journal of Neuroinflammation
Majid Ghareghani, Kazem Zibara, Hossein Sadeghi, Naser Farhadi
Multiple sclerosis (MS) is a progressive inflammatory demyelinating disease in the central nervous system (CNS). Melatonin is an effective treatment in MS patients and experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Melatonin secretion peaks at 2 AM, concomitant with the time at which the muscles are resting and the body is exerting its antioxidant activity. The current study was designed to investigate combination treatment of baclofen, a muscle relaxant drug, and melatonin in EAE mice...
March 1, 2018: Cellular and Molecular Neurobiology
Sahar Sheykhansari, Kristen Kozielski, Joachim Bill, Metin Sitti, Donato Gemmati, Paolo Zamboni, Ajay Vikram Singh
The effect of redox metals such as iron and copper on multiple sclerosis and amyotrophic lateral sclerosis has been intensively studied. However, the origin of these disorders remains uncertain. This review article critically describes the physiology of redox metals that produce oxidative stress, which in turn leads to cascades of immunomodulatory alteration of neurons in multiple sclerosis and amyotrophic lateral sclerosis. Iron and copper overload has been well established in motor neurons of these diseases' lesions...
March 1, 2018: Cell Death & Disease
Iain Hargreaves, Nimesh Mody, John Land, Simon Heales
OBJECTIVES: Evidence of mitochondrial respiratory chain (MRC) dysfunction and oxidative stress has been implicated in the pathophysiology of multiple sclerosis (MS). However, at present, there is no reliable low invasive surrogate available to evaluate mitochondrial function in these patients. In view of the particular sensitivity of MRC complex IV to oxidative stress, the aim of this study was to assess blood mononuclear cell (BMNC) MRC complex IV activity in MS patients and compare these results to age matched controls and MS patients on β-interferon treatment...
February 20, 2018: Journal of Clinical Medicine
Raluca Ileana Mincu, Stefania Lucia Magda, Sorina Mihaila, Maria Florescu, Diana Janina Mihalcea, Andreea Velcea, Adela Chiru, Cristina Tiu, Bogdan Ovidiu Popescu, Mircea Cinteza, Dragos Vinereanu
Multiple sclerosis (MS), neurologic disease affecting young population, may cause cardiovascular dysfunction, due to autonomous nervous dysfunction, physical invalidity, increased oxidative stress, and systemic inflammatory status. However, cardiovascular function is rarely evaluated in these patients. We assessed left and right ventricular (LV and RV) function by 2D, 3D, tissue Doppler, and speckle tracking echocardiography, and vascular function by remodeling, stiffness, and endothelial dysfunction parameters in patients with MS, compared to control subjects...
February 19, 2018: Scientific Reports
Ting Long, Yuan Yang, Ling Peng, Zuoxiao Li
Multiple sclerosis (MS) is a chronic auto-inflammatory disease of the central nervous system (CNS) and hard to heal. This study aimed to investigate the effect of melatonin on mice with experimental autoimmune encephalomyelitis (EAE), a widely used MS model, and its potential mechanism underlying the action of MT on anti-oxidative stress. Female C57BL/6 mice were injected with MOG35-55 peptide to set up the EAE model, and for detection of the effect of melatonin (10 mg/kg i.p.) on the development and progression of EAE...
February 15, 2018: Journal of Molecular Neuroscience: MN
Anne Vejux, Amira Namsi, Thomas Nury, Thibault Moreau, Gérard Lizard
Amyotrophic lateral sclerosis (ALS) is a non-demyelinating neurodegenerative disease in adults with motor disorders. Two forms exist: a sporadic form (90% of cases) and a family form due to mutations in more than 20 genes including the Superoxide dismutase 1, TAR DNA Binding Protein, Fused in Sarcoma, chromosome 9 open reading frame 72 and VAPB genes. The mechanisms associated with this pathology are beginning to be known: oxidative stress, glutamate excitotoxicity, protein aggregation, reticulum endoplasmic stress, neuroinflammation, alteration of RNA metabolism...
2018: Frontiers in Molecular Neuroscience
Tingting Wang, Lingling Liu, Xuyong Chen, Yuqing Shen, Gaojian Lian, Nilay Shah, Andrew M Davidoff, Jun Yang, Ruoning Wang
Heightened aerobic glycolysis and glutaminolysis are characteristic metabolic phenotypes in cancer cells. Neuroblastoma (NBL), a devastating pediatric cancer, is featured by frequent genomic amplification of MYCN, a member of the Myc oncogene family that is primarily expressed in the early stage of embryonic development and required for neural crest development. Here we report that an enriched glutaminolysis gene signature is associated with MYCN amplification in children with NBL. The partial knockdown of MYCN suppresses glutaminolysis in NBL cells...
February 14, 2018: Cell Death & Disease
Zhihui Zhu, Georg Reiser
Small heat shock proteins (sHsps) are a group of proteins with molecular mass between 12 and 43 kDa. Currently, 11 members of this family have been classified, namely HspB1 to HspB11. HspB1, HspB2, HspB5, HspB6, HspB7, and HspB8, which are expressed in brain have been observed to be related to the pathology of neurodegenerative diseases, including Parkinson's, Alzheimer's, Alexander's disease, multiple sclerosis, and human immunodeficiency virus-associated dementia. Specifically, sHsps interact with misfolding and damaging protein aggregates, like Glial fibrillary acidic protein in AxD, β-amyloid peptides aggregates in Alzheimer's disease, Superoxide dismutase 1 in Amyotrophic lateral sclerosis and cytosine-adenine-guanine/polyglutamine (CAG/PolyQ) in Huntington's disease, Spinocerebellar ataxia type 3, Spinal-bulbar muscular atrophy, to reduce the toxicity or increase the clearance of these protein aggregates...
February 6, 2018: Neurochemistry International
Xinyue Hu, Mohanraj Rajesh, Jian Zhang, Shanshan Zhou, Shudong Wang, Jian Sun, Yi Tan, Yang Zheng, Lu Cai
Oxidative stress and inflammation play key roles in the development of diabetic cardiomyopathy (DCM). Dimethyl fumarate (DMF), an FDA approved medicine for relapsing multiple sclerosis, has manifested its antioxidant and anti-inflammatory function mostly in the central nervous system. In this study, we investigated whether DMF could attenuate the development of DCM. Type 1 diabetes mouse model was established using multiple low-dose streptozotocin, and the diabetic mice were treated with DMF (10 mg/kg body weight) for 3 months...
February 2, 2018: Toxicology Letters
Alireza Abdanipour, Iraj Jafari Anarkooli, Saeed Shokri, Mehrdad Ghorbanlou, Vahid Bayati, Reza Nejatbakhsh
Oxidative stress and reactive oxygen species generation have been implicated in the pathogenesis of several neurological disorders including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis and multiple sclerosis. In the present study, the neuroprotective effects of selegiline against hydrogen peroxide-induced oxidative stress in hippocampus-derived neural stem cells (NSCs) were evaluated. NSCs isolated from neonatal Wistar rats were pretreated with different doses of selegiline for 48 h and then exposed to 125 µM H2O2 for 30 min...
January 2018: Biomedical Reports
Delphine Denoyer, Sharnel A S Clatworthy, Michael A Cater
Copper homeostasis is tightly regulated in both prokaryotic and eukaryotic cells to ensure sufficient amounts for cuproprotein biosynthesis, while limiting oxidative stress production and toxicity. Over the last century, copper complexes have been developed as antimicrobials and for treating diseases involving copper dyshomeostasis (e.g., Wilson's disease). There now exists a repertoire of copper complexes that can regulate bodily copper through a myriad of mechanisms. Furthermore, many copper complexes are now being appraised for a variety of therapeutic indications (e...
February 5, 2018: Metal Ions in Life Sciences
Ci-Di Chen, Ella Zeldich, Yuexuan Li, Andrea Yuste, Carmela R Abraham
Multiple lines of evidence show that the anti-aging and cognition-enhancing protein Klotho fosters neuronal survival, increases the anti-oxidative stress defense, and promotes remyelination of demyelinated axons. Thus, upregulation of the Klotho gene can potentially alleviate the symptoms and/or prevent the progression of age-associated neurodegenerative diseases such as Alzheimer's disease and demyelinating diseases such as multiple sclerosis. Here we used a CRISPR-dCas9 complex to investigate single-guide RNA (sgRNA) targeting the Klotho promoter region for efficient transcriptional activation of the Klotho gene...
February 2018: Journal of Molecular Neuroscience: MN
Heather M Francis, Richard J Stevenson
The pathophysiology of many neurological disorders involves oxidative stress, neuroinflammation, and mitochondrial dysfunction. There is now substantial evidence that diet can decrease these forms of pathophysiology, and an emerging body of literature relatedly suggests that diet can also prevent or even remediate the cognitive deficits observed in neurological disorders that exhibit such pathology (eg, Alzheimer's disease, multiple sclerosis, age-related cognitive decline, epilepsy). The current review summarizes the emerging evidence in relation to whole diets prominent in the scientific literature-ketogenic, caloric restriction, high polyphenol, and Mediterranean diets-and provides a discussion of the possible underlying neurophysiological mechanisms...
March 1, 2018: Nutrition Reviews
Giselle Pentón-Rol, Javier Marín-Prida, Viviana Falcón-Cama
Myelin loss has a crucial impact on behavior disabilities associated to Multiple Sclerosis (MS) and Ischemic Stroke (IS). Although several MS therapies are approved, none of them promote remyelination in patients, limiting their ability for chronic recovery. With no available therapeutic options, enhanced demyelination in stroke survivors is correlated with a poorer behavioral recovery. Here, we show the experimental findings of our group and others supporting the remyelinating effects of C-Phycocyanin (C-PC), the main biliprotein of Spirulina platensis and its linked tetrapyrrole Phycocyanobilin (PCB), in models of these illnesses...
January 18, 2018: Behavioral Sciences
Amalia Merelli, Julio Cesar Garcia Rodriguez, Jaume Folch, Marcelo R Regueiro, Antoni Camins, Lazarowski Alberto
Neurodegeneration (NDG) is linked with the progressive loss of neural function with intellectual and/or motor impairment. Several diseases affecting older individuals, including Alzheimer's disease, Amyotrophic Lateral Sclerosis, Huntington's disease, Parkinson's disease, stroke, Multiple Sclerosis and many others, are the most relevant disorders associated with NDG. Since other pathologies such as refractory epilepsy, brain infections, or hereditary diseases such as "neurodegeneration with brain iron accumulation", also lead to chronic brain inflammation with loss of neural cells, NDG can be said to affect all ages...
January 10, 2018: Current Neuropharmacology
Yasmeen M Taalab, Nour Ibrahim, Ahmed Maher, Mubashir Hassan, Wael Mohamed, Ahmed A Moustafa, Mohamed Salama, Dina Johar, Larry Bernstein
Neurodegenerative diseases, such as Alzheimer's disease, Huntington's disease, Parkinson's disease, prion disease, and amyotrophic lateral sclerosis, are a dissimilar group of disorders that share a hallmark feature of accumulation of abnormal intraneuronal or extraneuronal misfolded/unfolded protein and are classified as protein misfolding disorders. Cellular and endoplasmic reticulum (ER) stress activates multiple signaling cascades of the unfolded protein response (UPR). Consequently, translational and transcriptional alterations in target gene expression occur in response directed toward restoring the ER capacity of proteostasis and reestablishing the cellular homeostasis...
January 5, 2018: Reviews in the Neurosciences
Majel Cervantes-Llanos, Nielsen Lagumersindez-Denis, Javier Marín-Prida, Nancy Pavón-Fuentes, Viviana Falcon-Cama, Beatriz Piniella-Matamoros, Hanlet Camacho-Rodríguez, Julio Raúl Fernández-Massó, Carmen Valenzuela-Silva, Ivette Raíces-Cruz, Eduardo Pentón-Arias, Mauro Martins Teixeira, Giselle Pentón-Rol
The only three oral treatments currently available for multiple sclerosis (MS) target the relapsing forms of the disease and concerns regarding efficacy, safety and tolerability limit their use. Identifying novel oral disease-modifying therapies for MS, targeting both its inflammatory and neurodegenerative components is still a major goal. AIM: The scope of this study was to provide evidence that the oral administration of C-Phycocyanin (C-PC), the main biliprotein of the Spirulina platensis cyanobacteria and its tetrapyrrolic prosthetic group, Phycocyanobilin (PCB), exert ameliorating actions on rodent models of experimental autoimmune encephalomyelitis (EAE)...
December 26, 2017: Life Sciences
Simon Faissner, Manoj Mishra, Deepak K Kaushik, Jianxiong Wang, Yan Fan, Claudia Silva, Gail Rauw, Luanne Metz, Marcus Koch, V Wee Yong
The treatment of progressive multiple sclerosis (MS) is unsatisfactory. One reason is that the drivers of disease, which include iron-mediated neurotoxicity, lymphocyte activity, and oxidative stress, are not simultaneously targeted. Here we present a systematic screen to identify generic, orally available medications that target features of progressive MS. Of 249 medications that cross the blood-brain barrier, 35 prevent iron-mediated neurotoxicity in culture. Of these, several antipsychotics and antidepressants strongly reduce T-cell proliferation and oxidative stress...
December 19, 2017: Nature Communications
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