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Neuroprotection in multiple sclerosis

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https://www.readbyqxmd.com/read/28497982/neuroprotection-in-oxidative-stress-related-neurodegenerative-diseases-role-of-endocannabinoid-system-modulation
#1
Janos Paloczi, Zoltan V Varga, George Hasko, Pal Pacher
SIGNIFICANCE: Redox imbalance may lead to overproduction of reactive oxygen and nitrogen species (ROS/RNS) and subsequent oxidative tissue damage which is a critical event in the course of neurodegenerative diseases. It is still not fully elucidated, however, whether oxidative stress is the primary trigger or a consequence in process of neurodegeneration. Recent Advances: Increasing evidence suggests that oxidative stress is involved in the propagation of neuronal injury and consequent inflammatory response, which in concert promote development of pathological alterations characteristic of most common neurodegenerative diseases...
May 12, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28497312/phenytoin-neuroprotection-or-neurotoxicity
#2
REVIEW
Jan M Keppel Hesselink, David J Kopsky
Phenytoin is an 80-year young molecule and new indications are still emerging. The neuroprotective potential of phenytoin has been evaluated for decades. Recently, a positive phase II trial supported its further development in the treatment of optic neuritis in multiple sclerosis. In 1942, however, peripheral neuritis was first reported to be an adverse event of phenytoin, and since then a small but steady stream of publications discussed peripheral polyneuropathy as being a possible adverse event of phenytoin...
May 11, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28473732/anti-inflammatory-and-neuroprotective-role-of-natural-product-securinine-in-activated-glial-cells-implications-for-parkinson-s-disease
#3
Dmitri Leonoudakis, Anand Rane, Suzanne Angeli, Gordon J Lithgow, Julie K Andersen, Shankar J Chinta
Glial activation and subsequent release of neurotoxic proinflammatory factors are believed to play an important role in the pathogenesis of several neurological disorders including Parkinson's disease (PD). Inhibition of glial activation and inflammatory processes may represent a therapeutic target to alleviate neurodegeneration. Securinine, a major natural alkaloid product from the root of the plant Securinega suffruticosa, has been reported to have potent biological activity and is used in the treatment of neurological conditions such as amyotrophic lateral sclerosis, poliomyelitis, and multiple sclerosis...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28466274/neural-stem-cell-based-regenerative-approaches-for-the-treatment-of-multiple-sclerosis
#4
REVIEW
Juan Xiao, Rongbing Yang, Sangita Biswas, Yunhua Zhu, Xin Qin, Min Zhang, Lihong Zhai, Yi Luo, Xiaoming He, Chun Mao, Wenbin Deng
Multiple sclerosis (MS) is a chronic, autoimmune, inflammatory, and demyelinating disorder of the central nervous system (CNS), which ultimately leads to axonal loss and permanent neurological disability. Current treatments for MS are largely comprised of medications that are either immunomodulatory or immunosuppressive and are aimed at reducing the frequency and intensity of relapses. Neural stem cells (NSCs) in the adult brain can differentiate into oligodendrocytes in a context-specific manner and are shown to be involved in the remyelination in these patients...
May 2, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28464811/effect-of-catalpol-on-remyelination-through-experimental-autoimmune-encephalomyelitis-acting-to-promote-olig1-and-olig2-expressions-in-mice
#5
Tao Yang, Qi Zheng, Su Wang, Ling Fang, Lei Liu, Hui Zhao, Lei Wang, Yongping Fan
BACKGROUND: Multiple sclerosis (MS) as an autoimmune disorder is a common disease occurring in central nervous system (CNS) and the remyelination plays a pivotal role in the alleviating neurological impairment in the MS. Catalpol, an effective component extracted from the Chinese herb Radix Rehmanniae, which has been proved protective in cerebral diseases. METHODS: To determine the protective effects and mechanisms of Catalpol on MS, the mice with experimental autoimmune encephalomyelitis (EAE) were induced by myelin oligodendrocyte glycoprotein (MOG) 35-55, as a model for human MS...
May 2, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28456941/activation-of-glucagon-like-peptide-1-receptor-promotes-neuroprotection-in-experimental-autoimmune-encephalomyelitis-by-reducing-neuroinflammatory-responses
#6
Chi-Ho Lee, Se Jin Jeon, Kyu Suk Cho, Eunjung Moon, Arjun Sapkota, Hee Sook Jun, Jong Hoon Ryu, Ji Woong Choi
The signaling axis of glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) has been an important component in overcoming diabetes, and recent reports have uncovered novel beneficial roles of this signaling axis in central nervous system (CNS) disorders, such as Alzheimer's disease, Parkinson's disease, and cerebral ischemia, accelerating processes for exendin-4 repositioning. Here, we studied whether multiple sclerosis (MS) could be a complement to the CNS disorders that are associated with the GLP-1/GLP-1R signaling axis...
April 29, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28456633/optineurin-in-amyotrophic-lateral-sclerosis-multifunctional-adaptor-protein-at-the-crossroads-of-different-neuroprotective-mechanisms
#7
REVIEW
Andrea Markovinovic, Raffaello Cimbro, Tereza Ljutic, Jasna Kriz, Boris Rogelj, Ivana Munitic
When optineurin mutations showed up on the amyotrophic lateral sclerosis (ALS) landscape in 2010, they differed from most other ALS-causing genes. They seemed to act by loss- rather than gain-of-function, and it was unclear how a polyubiquitin-binding adaptor protein, which was proposed to regulate a variety of cellular functions including cell signaling and vesicle trafficking, could mediate neuroprotection. This review discusses the considerable progress that has been made since then. A large number of mutations in optineurin and optineurin-interacting proteins TANK-binding kinase (TBK1) and p62/SQSTM-1 have been found in the ALS patients, suggesting a common neuroprotective pathway...
April 26, 2017: Progress in Neurobiology
https://www.readbyqxmd.com/read/28447514/neuroprotective-effects-of-ellagic-acid-on-cuprizone-induced-acute-demyelination-through-limitation-of-microgliosis-adjustment-of-cxcl12-il-17-il-11-axis-and-restriction-of-mature-oligodendrocytes-apoptosis
#8
Nima Sanadgol, Fereshteh Golab, Zakiyeh Tashakkor, Nooshin Taki, Samira Moradi Kouchi, Ali Mostafaie, Mehdi Mehdizadeh, Mohammad Abdollahi, Ghorban Taghizadeh, Mohammad Sharifzadeh
CONTEXT: Ellagic acid (EA) is a natural phenol antioxidant with various therapeutic activities. However, the efficacy of EA has not been examined in neuropathologic conditions. OBJECTIVE: In vivo neuroprotective effects of EA on cuprizone (cup)-induced demyelination were evaluated. MATERIAL AND METHODS: C57BL/6 J mice were fed with chow containing 0.2% cup for 4 weeks to induce oligodendrocytes (OLGs) depletion predominantly in the corpus callosum (CC)...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28423529/pif-promotes-brain-re-myelination-locally-while-regulating-systemic-inflammation-clinically-relevant-multiple-sclerosis-m-smegmatis-model
#9
Giuseppe Migliara, Martin Mueller, Alessia Piermattei, Chaya Brodie, Michael J Paidas, Eytan R Barnea, Francesco Ria
Neurologic disease diagnosis and treatment is challenging. Multiple Sclerosis (MS) is a demyelinating autoimmune disease with few clinical forms and uncertain etiology. Current studies suggest that it is likely caused by infection(s) triggering a systemic immune response resulting in antigen/non-antigen-related autoimmune response in central nervous system (CNS). New therapeutic approaches are needed. Secreted by viable embryos, PreImplantation Factor (PIF) possesses a local and systemic immunity regulatory role...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422748/therapeutic-inhibition-of-soluble-brain-tnf-promotes-remyelination-by-increasing-myelin-phagocytosis-by-microglia
#10
Maria Karamita, Christopher Barnum, Wiebke Möbius, Malú G Tansey, David E Szymkowski, Hans Lassmann, Lesley Probert
Multiple sclerosis (MS) is an inflammatory CNS demyelinating disease in which remyelination largely fails. Transmembrane TNF (tmTNF) and TNF receptor 2 are important for remyelination in experimental MS models, but it is unknown whether soluble TNF (solTNF), a major proinflammatory factor, is involved in regeneration processes. Here, we investigated the specific contribution of solTNF to demyelination and remyelination in the cuprizone model. Treatment with XPro1595, a selective inhibitor of solTNF that crosses the intact blood-brain barrier (BBB), in cuprizone-fed mice did not prevent toxin-induced oligodendrocyte loss and demyelination, but it permitted profound early remyelination due to improved phagocytosis of myelin debris by CNS macrophages and prevented disease-associated decline in motor performance...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28412918/neurological-aspects-of-medical-use-of-cannabidiol
#11
Carmen Mannucci, Michele Navarra, Fabrizio Calapai, Elvira Ventura Spagnolo, Francesco Paolo Busardò, Roberto Da Cas, Francesca Menniti Ippolito, Gioacchino Calapai
BACKGROUND: Cannabidiol (CBD) is among the major secondary metabolites of Cannabis devoid of the delta-9-tetra-hydrocannabinol psychoactive effects. It is a resorcinol-based compound with a broad spectrum of potential therapeutic properties, including neuroprotective effects in numerous pathological conditions. CBD neuroprotection is due to its antioxidant and antiinflammatory activi-ties and the modulation of a large number of brain biological targets (receptors, channels) involved in the development and maintenance of neurodegenerative diseases...
April 13, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28397112/cell-therapy-for-multiple-sclerosis
#12
REVIEW
Pamela Sarkar, Claire M Rice, Neil J Scolding
Cell therapy is considered a promising potential treatment for multiple sclerosis, perhaps particularly for the progressive form of the disease for which there are currently no useful treatments. Over the past two decades or more, much progress has been made in understanding the biology of MS and in the experimental development of cell therapy for this disease. Three quite distinct forms of cell therapy are currently being pursued. The first seeks to use stem cells to replace damaged myelin-forming oligodendrocytes within the CNS; the second aims, in effect, to replace the individual's misfunctioning immune system, making use of haematopoietic stem cells; and the third seeks to utilise endogenous stem cell populations by mobilisation with or without in vitro expansion, exploiting their various reparative and neuroprotective properties...
April 10, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28394203/dysregulation-of-energy-metabolism-in-multiple-sclerosis-measured-in-vivo-with-diffusion-weighted-spectroscopy
#13
Benedetta Bodini, Francesca Branzoli, Emilie Poirion, Daniel García-Lorenzo, Mélanie Didier, Elisabeth Maillart, Julie Socha, Geraldine Bera, Catherine Lubetzki, Itamar Ronen, Stephane Lehericy, Bruno Stankoff
OBJECTIVE: We employed diffusion-weighted magnetic resonance spectroscopy (DW-MRS), which allows to measure in vivo the diffusion properties of metabolites, to explore the functional neuro-axonal damage and the ongoing energetic dysregulation in multiple sclerosis (MS). METHODS: Twenty-five patients with MS and 18 healthy controls (HC) underwent conventional magnetic resonance imaging (MRI) and DW-MRS. The apparent diffusion coefficient (ADC) of total N-acetyl-aspartate (tNAA) and creatine-phosphocreatine (tCr) were measured in the parietal normal-appearing white matter (NAWM) and in the thalamic grey matter (TGM)...
April 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28387380/a-staged-screening-of-registered-drugs-highlights-remyelinating-drug-candidates-for-clinical-trials
#14
C Eleuteri, S Olla, C Veroni, R Umeton, R Mechelli, S Romano, M C Buscarinu, F Ferrari, G Calò, G Ristori, M Salvetti, C Agresti
There is no treatment for the myelin loss in multiple sclerosis, ultimately resulting in the axonal degeneration that leads to the progressive phase of the disease. We established a multi-tiered platform for the sequential screening of drugs that could be repurposed as remyelinating agents. We screened a library of 2,000 compounds (mainly Food and Drug Administration (FDA)-approved compounds and natural products) for cellular metabolic activity on mouse oligodendrocyte precursors (OPC), identifying 42 molecules with significant stimulating effects...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28381594/nimodipine-fosters-remyelination-in-a-mouse-model-of-multiple-sclerosis-and-induces-microglia-specific-apoptosis
#15
Andrea Schampel, Oleg Volovitch, Tobias Koeniger, Claus-Jürgen Scholz, Stefanie Jörg, Ralf A Linker, Erhard Wischmeyer, Marie Wunsch, Johannes W Hell, Süleyman Ergün, Stefanie Kuerten
Despite continuous interest in multiple sclerosis (MS) research, there is still a lack of neuroprotective strategies, because the main focus has remained on modulating the immune response. Here we performed in-depth analysis of neurodegeneration in experimental autoimmune encephalomyelitis (EAE) and in in vitro studies regarding the effect of the well-established L-type calcium channel antagonist nimodipine. Nimodipine treatment attenuated clinical EAE and spinal cord degeneration and promoted remyelination...
April 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28374232/monitoring-the-course-of-ms-with-optical-coherence-tomography
#16
REVIEW
Alexander U Brandt, Elena H Martinez-Lapiscina, Rachel Nolan, Shiv Saidha
Retinae of patients with multiple sclerosis (MS), as part of the central nervous system (CNS), display inflammatory and neurodegenerative changes. There is increasing evidence suggesting that retinal changes, and in particular neurodegeneration, mirror global CNS alterations in MS. Spectral domain optical coherence tomography (SD-OCT) is an inexpensive, rapid, non-invasive, and reproducible imaging technique that generates high-resolution images of tissues such as the retina. An advantage of SD-OCT over magnetic resonance imaging techniques in the assessment of neurodegeneration may be its sensitivity to capture changes at the individual patient level...
April 2017: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/28369944/increasing-acetyl-coa-metabolism-attenuates-injury-and-alters-spinal-cord-lipid-content-in-mice-subjected-to-experimental-autoimmune-encephalomyelitis
#17
Amber C Chevalier, Thad A Rosenberger
Acetate supplementation increases brain acetyl-CoA metabolism, alters histone and non-histone protein acetylation, increases brain energy reserves, and is anti-inflammatory and neuroprotective in rat models of neuroinflammation and neuroborreliosis. To determine the impact acetate supplementation has on a mouse model of multiple sclerosis, we quantified the effect treatment had on injury progression, spinal cord lipid content, phospholipase levels, and myelin structure in mice subjected to experimental autoimmune encephalomyelitis (EAE)...
March 31, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28363412/fty720-derivatives-do-not-induce-fty720-like-lymphopenia
#18
Ismael Segura-Ulate, Troy K Belcher, Guadalupe Vidal-Martinez, Javier Vargas-Medrano, Ruth G Perez
FTY720 is an immunosuppressive multiple sclerosis (MS) drug that stimulates the expression of neuroprotective brain-derived-neurotrophic-factor (BDNF). In vivo preclinical data suggest that FTY720 could be beneficial for treating Parkinson's patients, though its immunosuppressive effects might limit its efficacy. Two novel FTY720-derivatives, FTY720-C2 and FTY720-Mitoxy, also stimulate BDNF expression and enter brain like FTY720 but are not phosphorylated, suggesting they will not produce FTY720-like immunosuppression...
March 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28362719/imaging-markers-of-multiple-sclerosis-prognosis
#19
Céline Louapre, Benedetta Bodini, Catherine Lubetzki, Léorah Freeman, Bruno Stankoff
PURPOSE OF REVIEW: Studies of large longitudinal cohorts of patients with multiple sclerosis (MS) have emphasized the prognostic value of conventional MRI markers, at least during early stages. Advanced imaging metrics derived from quantitative MRI and PET provide relevant information about microstructural damage within and outside visible lesions that may be more sensitive to predict long-term disability. Here, we summarize the most recent findings regarding the prognostic value of imaging markers throughout MS stages...
June 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28350081/morroniside-protects-sk-n-sh-human-neuroblastoma-cells-against-h2o2-induced-damage
#20
Jing-Xing Zhang, Rui Wang, Jin Xi, Lin Shen, An-You Zhu, Qi Qi, Qi-Yi Wang, Lun-Jun Zhang, Feng-Chao Wang, He-Zuo Lü, Jian-Guo Hu
Oxidative stress-induced cell injury has been linked to the pathogenesis of neurodegenerative disorders such as spinal cord injury, Parkinson's disease, and multiple sclerosis. Morroniside is an antioxidant derived from the Chinese herb Shan-Zhu-Yu. The present study investigated the neuroprotective effect of morroniside against hydrogen peroxide (H2O2)-induced cell death in SK-N-SH human neuroblastoma cells. H2O2 increased cell apoptosis, as determined by flow cytometry and Hoechst 33342 staining. This effect was reversed by pretreatment with morroniside at concentrations of 1-100 µM...
February 8, 2017: International Journal of Molecular Medicine
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