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Neuroprotection in multiple sclerosis

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https://www.readbyqxmd.com/read/28726788/neuroprotection-by-eif2%C3%AE-chop-inhibition-and-xbp-1-activation-in-eae-optic-neuritiss
#1
Haoliang Huang, Linqing Miao, Feisi Liang, Xiaodong Liu, Lin Xu, Xiuyin Teng, Qizhao Wang, William H Ridder, Kenneth S Shindler, Yang Sun, Yang Hu
No therapies exist to prevent neuronal deficits in multiple sclerosis (MS), because the molecular mechanism responsible for the progressive neurodegeneration is unknown. We previously showed that axon injury-induced neuronal endoplasmic reticulum (ER) stress plays an important role in retinal ganglion cell (RGC) death and optic nerve degeneration in traumatic and glaucomatous optic neuropathies. Optic neuritis, one of the most common clinical manifestations of MS, is readily modeled by experimental autoimmune encephalomyelitis (EAE) in mouse...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28702353/longitudinal-mr-spectroscopy-of-neurodegeneration-in-multiple-sclerosis-with-diffusion-of-the-intra-axonal-constituent-n-acetylaspartate
#2
Emily Turner Wood, Ece Ercan, Pascal Sati, Irene C M Cortese, Itamar Ronen, Daniel S Reich
Multiple sclerosis (MS) is a pathologically complex CNS disease: inflammation, demyelination, and neuroaxonal degeneration occur concurrently and may depend on one another. Current therapies are aimed at the immune-mediated, inflammatory destruction of myelin, whereas axonal degeneration is ongoing and not specifically targeted. Diffusion-weighted magnetic resonance spectroscopy can measure the diffusivity of metabolites in vivo, such as the axonal/neuronal constituent N-acetylaspartate, allowing compartment-specific assessment of disease-related changes...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28697282/exploring-the-potential-of-natural-and-synthetic-neuroprotective-steroids-against-neurodegenerative-disorders-a-literature-review
#3
REVIEW
Ranju Bansal, Ranjit Singh
Neurodegeneration is a complex process, which leads to progressive brain damage due to loss of neurons. Despite exhaustive research, the cause of neuronal loss in various degenerative disorders is not entirely understood. Neuroprotective steroids constitute an important line of attack, which could play a major role against the common mechanisms associated with various neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Natural endogenous steroids induce the neuroprotection by protecting the nerve cells from neuronal injury through multiple mechanisms, therefore the structural modifications of the endogenous steroids could be helpful in the generation of new therapeutically useful neuroprotective agents...
July 11, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28694434/laquinimod-treatment-in-the-r6-2-mouse-model
#4
Gisa Ellrichmann, Alina Blusch, Oluwaseun Fatoba, Janine Brunner, Liat Hayardeny, Michael Hayden, Dominik Sehr, Konstanze F Winklhofer, Carsten Saft, Ralf Gold
The transgenic mouse model R6/2 exhibits Huntington's disease (HD)-like deficits and basic pathophysiological similarities. We also used the pheochromocytoma-12 (PC12)-cell-line-model to investigate the effect of laquinimod on metabolic activity. Laquinimod is an orally administered immunomodulatory substance currently under development for the treatment of multiple sclerosis (MS) and HD. As an essential effect, increased levels of BDNF were observed. Therefore, we investigated the therapeutic efficacy of laquinimod in the R6/2 model, focusing on its neuroprotective capacity...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28680531/mitochondrial-uncoupler-prodrug-of-2-4-dinitrophenol-mp201-prevents-neuronal-damage-and-preserves-vision-in-experimental-optic-neuritis
#5
Reas S Khan, Kimberly Dine, John G Geisler, Kenneth S Shindler
The ability of novel mitochondrial uncoupler prodrug of 2,4-dinitrophenol (DNP), MP201, to prevent neuronal damage and preserve visual function in an experimental autoimmune encephalomyelitis (EAE) model of optic neuritis was evaluated. Optic nerve inflammation, demyelination, and axonal loss are prominent features of optic neuritis, an inflammatory optic neuropathy often associated with the central nervous system demyelinating disease multiple sclerosis. Currently, optic neuritis is frequently treated with high-dose corticosteroids, but treatment fails to prevent permanent neuronal damage and associated vision changes that occur as optic neuritis resolves, thus suggesting that additional therapies are required...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28677678/srsf1-dependent-nuclear-export-inhibition-of-c9orf72-repeat-transcripts-prevents-neurodegeneration-and-associated-motor-deficits
#6
Guillaume M Hautbergue, Lydia M Castelli, Laura Ferraiuolo, Alvaro Sanchez-Martinez, Johnathan Cooper-Knock, Adrian Higginbottom, Ya-Hui Lin, Claudia S Bauer, Jennifer E Dodd, Monika A Myszczynska, Sarah M Alam, Pierre Garneret, Jayanth S Chandran, Evangelia Karyka, Matthew J Stopford, Emma F Smith, Janine Kirby, Kathrin Meyer, Brian K Kaspar, Adrian M Isaacs, Sherif F El-Khamisy, Kurt J De Vos, Ke Ning, Mimoun Azzouz, Alexander J Whitworth, Pamela J Shaw
Hexanucleotide repeat expansions in the C9ORF72 gene are the commonest known genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Expression of repeat transcripts and dipeptide repeat proteins trigger multiple mechanisms of neurotoxicity. How repeat transcripts get exported from the nucleus is unknown. Here, we show that depletion of the nuclear export adaptor SRSF1 prevents neurodegeneration and locomotor deficits in a Drosophila model of C9ORF72-related disease. This intervention suppresses cell death of patient-derived motor neuron and astrocytic-mediated neurotoxicity in co-culture assays...
July 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28676349/immunoregulatory-effect-of-mast-cells-influenced-by-microbes-in-neurodegenerative-diseases
#7
Francesco Girolamo, Coppola Cristiana Coppola, Domenico Ribatti
When related to central nervous system (CNS) health and disease, brain mast cells (MCs) can be a source of either beneficial or deleterious signals acting on neural cells. We review the current state of knowledge about molecular interactions between MCs and glia in neurodegenerative diseases such as Multiple Sclerosis, Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, epilepsy. We also discuss the influence on MC actions evoked by the host microbiota, which has a profound effect on the host immune system, inducing important consequences in neurodegenerative disorders...
July 1, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28675779/neurosteroidogenesis-and-progesterone-anti-inflammatory-neuroprotective-effects
#8
REVIEW
Alejandro F De Nicola, Laura I Garay, Maria Meyer, Rachida Guennoun, Regine Sitruk-Ware, Michael Schumacher, Maria Claudia Gonzalez Deniselle
Progesterone shows anti-inflammatory and promyelinating effects in mice with autoimmune experimental encephalomyelitis (EAE), a commonly used model for multiple sclerosis (MS). Since neurosteroids have been implicated as protective factors for MS and EAE, we analyzed the expression of neurosteroidogenic enzymes in the compromised spinal cord of EAE mice. EAE was induced in female C57Bl6 mice and killed on day 16 after induction. Progesterone was given by pellet implantation 1 week before EAE induction. Untreated EAE mice showed decreased mRNAs for the steroidogenic acute regulatory protein (Star), voltage-dependent anion channel (VDAC), cholesterol side-chain cleavage (P450scc), 5α-reductase, 3α-hydroxysteroid dehydrogenase (3α-HSOR) and aromatase, whereas changes of 3β-hydroxysteroid dehydrogenase (3β-HSD) were not significant...
July 4, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28675259/review-of-the-novelties-from-the-32nd-ectrims-congress-2016-presented-at-the-9th-post-ectrims-meeting-ii
#9
REVIEW
O Fernandez, A Oterino, C Oreja-Guevara, J M Prieto, M M Mendibe-Bilbao, J A Garcia-Merino, Ll Ramio-Torrenta, R Ginestal, J E Meca-Lallana, L Romero-Pinel, D Munoz, P Oliva-Nacarino, M C Calles-Hernandez, G Izquierdo, M L Martinez-Gines, A Saiz, M Comabella, B Casanova-Estruch, Ll Brieva, R Arroyo, A Rodriguez-Antiguedad
For the ninth year in a row the Post-ECTRIMS Meeting has been held in Madrid (Spain) with the aim of presenting and discussing the hottest issues debated at the ECTRIMS Congress by renowned specialists in multiple sclerosis in our country. One outcome of this scientific activity, endorsed by the Spanish Neurology Society, is this review article, which is published in two parts. This second part reflects the current controversy over the management of multiple sclerosis, especially as regards the progressive forms and their differential diagnosis...
July 16, 2017: Revista de Neurologia
https://www.readbyqxmd.com/read/28668079/effects-of-bu-shen-yi-sui-capsule-on-nogoa-ngr-and-its-signaling-pathways-rhoa-rock-in-mice-with-experimental-autoimmune-encephalomyelitis
#10
Ling Fang, Yongqiang Wang, Qi Zheng, Tao Yang, Peiyuan Zhao, Hui Zhao, Qiuxia Zhang, Yuanyuan Zhao, Fang Qi, Kangning Li, Zhenzhen Chen, Junling Li, Nan Zhang, Yongping Fan, Lei Wang
BACKGROUND: Axon growth inhibitory factors NogoA/Nogo receptor (NgR) and its signaling pathways RhoA/Rho kinase (ROCK) play a critical role in the repair of nerve damage in multiple sclerosis (MS). Bu Shen Yi Sui Capsule (BSYSC) is an effective Chinese formula utilized to treat MS in clinical setting and noted for its potent neuroprotective effects. In this study, we focus on the effects of BSYSC on promoting nerve repair and the underlying mechanisms in mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS...
July 1, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28655617/the-effects-of-berberine-on-a-murine-model-of-multiple-sclerosis-and-the-sphk1-s1p-signaling-pathway
#11
Jiaming Luo, Rong Chen, Siyu Zeng, Juming Yu, Guohui Jiang, Li Wang, Xinyue Qin
Berberine (BBR) has shown neuroprotective properties. The present study aims to investigate the effects of BBR on experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS), and SphK1/S1P signaling, which plays a key role in MS. EAE was induced in mice, followed by treatment with BBR at 50, 100, or 300 mg/kg/d. Neurophysiological function was evaluated daily; inflammation, cell infiltration, and the severity of demyelination were also examined. The SphK1, SphK2, and S1P levels in the animals and primary astrocyte culture were measured...
June 24, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28655310/protease-activated-receptor-1-activation-by-granzyme-b-causes-neurotoxicity-that-is-augmented-by-interleukin-1%C3%AE
#12
Paul R Lee, Tory P Johnson, Sharmilee Gnanapavan, Gavin Giovannoni, Tongguang Wang, Joseph P Steiner, Marie Medynets, Mark J Vaal, Valerie Gartner, Avindra Nath
BACKGROUND: The cause of neurodegeneration in progressive forms of multiple sclerosis is unknown. We investigated the impact of specific neuroinflammatory markers on human neurons to identify potential therapeutic targets for neuroprotection against chronic inflammation. METHODS: Surface immunocytochemistry directly visualized protease-activated receptor-1 (PAR1) and interleukin-1 (IL-1) receptors on neurons in human postmortem cortex in patients with and without neuroinflammatory lesions...
June 27, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28647405/docosahexaenoic-acid-promotes-oligodendrocyte-differentiation-via-ppar-%C3%AE-signalling-and-prevents-tumor-necrosis-factor-%C3%AE-dependent-maturational-arrest
#13
A Bernardo, M L Giammarco, C De Nuccio, M A Ajmone-Cat, S Visentin, R De Simone, L Minghetti
Docosahexaenoic acid (DHA) is an essential omega-3 fatty acid known to be neuroprotective in several models of human diseases, including multiple sclerosis. The protective effects of DHA are largely attributed to its ability to interfere with the activity of transcription factors controlling immune and inflammatory responses, including the agonist-dependent transcription factor peroxisome proliferator-activated receptor-γ (PPAR-γ). In this study, we used primary oligodendrocyte progenitor (OP) cultures from neonatal rat brain to investigate whether DHA could influence OP maturation and directly promote myelination, as previously reported for selective PPAR-γ agonists...
June 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28646409/neuroprotective-effects-of-g-csf-administration-in-microglia-mediated-reactive-t-cell-activation-in-vitro
#14
Wei Peng
G-CSF is a growth factor that has known neuroprotective effects in a variety of experimental brain injury models. As both antigen-presenting microglia and reactive T cells are key components in the development and progression of EAE, the aim of this study is to investigate the neuroprotective effects of recombinant human G-CSF, as administered in microglia-mediated reactive T cell assay in vitro. Our results indicate that G-CSF treatment has no apparent effect for the resting un-activated microglia. G-CSF pre-protection of microglia increased protective cytokine IL-4 production and effectively inhibited the productions of NO and other inflammatory mediators (IFN-γ, TNF-α, IL-1β, IL-17, and chemokine MCP-1) after LPS stimulation...
June 23, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28621170/therapeutic-efficacy-of-multipotent-adult-progenitor-cells-versus-mesenchymal-stem-cells-in-experimental-autoimmune-encephalomyelitis
#15
Saurabh Pratap Singh, Sachin Hanumantrao Jadhav, Chandra Prakash Chaturvedi, Soniya Nityanand
AIM: In this study, we have evaluated the therapeutic efficacy of mouse multipotent adult progenitor cells (mMAPCs) in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, and compared it with mouse mesenchymal stem cells (mMSCs). MATERIALS & METHODS: We administered PKH26-labeled mMAPC and mMSC into EAE mice and evaluated their therapeutic efficacy. RESULTS: The mMAPC-treated mice in comparison with the mMSC group exhibited a higher suppression of EAE (p < 0...
June 16, 2017: Regenerative Medicine
https://www.readbyqxmd.com/read/28619434/terminalia-chebula-attenuates-quinolinate-induced-oxidative-pc12-and-oln-93-cell-death
#16
Hamid R Sadeghnia, Roya Jamshidi, Amir R Afshari, Hamid Mollazadeh, Fatemeh Forouzanfar, Hasan Rakhshandeh
BACKGROUND: Quinolinic acid (QA) is a product of tryptophan degradation and its pathologic accumulation has been found to induce neuroinflammatory and demyelinating diseases such as multiple sclerosis via excessive free radicals generation. Recent studies showed that Terminalia chebula has several pharmacological effects such as antioxidant, anti-inflammatory and neuroprotective properties. The aim of this study was evaluation of the protective effect of T. chebula alcoholic extract (TCAE) on oxidative PC12 and OLN-93 cells death induced by QA...
May 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28608697/perspectives-of-cannabinoid-type-2-receptor-cb2r-ligands-in-neurodegenerative-disorders-structure-affinity-relationship-safir-and-structure-activity-relationship-sar-studies
#17
Francesco Spinelli, Elena Capparelli, Carmen Abate, Nicola A Colabufo, Marialessandra Contino
Up-regulation of CB2R on activated microglial cells, the first step in neurodegeneration, has been widely demonstrated, and this finding makes the receptor a promising target in the early diagnosis and treatment of several neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and multiple sclerosis (MS). The development of CB2R PET ligands could help demonstrate the neurodegenerative pathogenesis, thus providing useful tools for characterizing the role of neuroinflammation in the progression of these disorders...
June 13, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28601278/laquinimod-has-no-effects-on-brain-volume-or-cellular-cns-composition-in-the-f1-3xtg-ad-c3h-mouse-model-of-alzheimer-s-disease
#18
Rehana Z Hussain, William A Miller-Little, Doris Lambracht-Washington, Tom C Jaramillo, Masaya Takahashi, Shanrong Zhang, Min Fu, Gary R Cutter, Liat Hayardeny, Craig M Powell, Roger N Rosenberg, Olaf Stüve
BACKGROUND: Laquinimod is an anti-inflammatory agent with good central nervous system (CNS) bioavailability, and neuroprotective and myelorestorative properties. A clinical trial in patients with multiple sclerosis demonstrated that laquinimod significantly reduced loss of brain volume. The cellular substrate or molecular events underlying that treatment effect are unknown. In this study, we aimed to explore laquinimod's potential effects on brain volume, animal behavior, cellular numbers and composition of CNS-intrinsic cells and mononuclear cells within the CNS, amyloid beta (Aβ) accumulation and tau phosphorylation in the F1 3xTg-AD/C3H mouse model of Alzheimer's disease...
August 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28580582/modulating-inflammation-and-neuroprotection-in-multiple-sclerosis
#19
REVIEW
Heather Yong, Gabrielle Chartier, Jacqueline Quandt
Multiple sclerosis (MS) is a neurological disorder of the central nervous system with a presentation and disease course that is largely unpredictable. MS can cause loss of balance, impaired vision or speech, weakness and paralysis, fatigue, depression, and cognitive impairment. Immunomodulation is a major target given the appearance of focal demyelinating lesions in myelin-rich white matter, yet progression and an increasing appreciation for gray matter involvement, even during the earliest phases of the disease, highlights the need to afford neuroprotection and limit neurodegenerative processes that correlate with disability...
June 5, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28578514/the-beneficial-effects-of-hmg-coa-reductase-inhibitors-in-the-processes-of-neurodegeneration
#20
REVIEW
Seyed Soheil Saeedi Saravi, Seyed Sobhan Saeedi Saravi, Alireza Arefidoust, Ahmad Reza Dehpour
Statins, cholesterol lowering drugs, have been demonstrated to exert beneficial effects in other conditions such as primary and progressing neurodegenerative diseases beyond their original role. Observation that statins ameliorate the neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS) and cerebral ischemic stroke, the neuroprotective effects of these drugs are thought to be linked to their anti-inflammatory, anti-oxidative, and anti-excitotoxic properties...
August 2017: Metabolic Brain Disease
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