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Neuroprotection in multiple sclerosis

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https://www.readbyqxmd.com/read/28204825/morroniside-protects-sk-n-sh-human-neuroblastoma-cells-against-h2o2-induced-damage
#1
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...
March 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28197174/extremely-low-frequency-electromagnetic-fields-stimulation-modulates-autoimmunity-and-immune-responses-a-possible-immuno-modulatory-therapeutic-effect-in-neurodegenerative-diseases
#2
REVIEW
Fabio Guerriero, Giovanni Ricevuti
Increasing evidence shows that extremely low frequency electromagnetic fields (ELF-EMFs) stimulation is able to exert a certain action on autoimmunity and immune cells. In the past, the efficacy of pulsed ELF-EMFs in alleviating the symptoms and the progression of multiple sclerosis has been supported through their action on neurotransmission and on the autoimmune mechanisms responsible for demyelination. Regarding the immune system, ELF-EMF exposure contributes to a general activation of macrophages, resulting in changes of autoimmunity and several immunological reactions, such as increased reactive oxygen species-formation, enhanced phagocytic activity and increased production of chemokines...
December 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/28163215/vegf-alleviates-als-csf-induced-cytoplasmic-accumulations-of-tdp-43-and-fus-tls-in-nsc-34-cells
#3
Shubham Shantanu, K Vijayalakshmi, S Shruthi, B K Chandrasekhar Sagar, T N Sathyaprabha, A Nalini, Trichur R Raju, Phalguni Anand Alladi
Cytoplasmic mislocalisation and aggregation of TDP-43 and FUS/TLS proteins in spinal motor neurons contribute to the pathogenesis of the highly fatal disorder amyotrophic lateral sclerosis (ALS). We investigated the neuroprotective effect of VEGF on expression of these proteins in the motor neuronal cell line NSC-34 modelled to reminisce sporadic form of ALS. We studied the expression of TDP-43 and FUS/TLS proteins after exposure to ALS-CSF and following VEGF supplementation by quantitative confocal microscopy and electron microscopy...
February 2, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28160128/blockade-of-the-kinin-b1-receptor-affects-the-cytokine-chemokine-profile-in-rat-brain-subjected-to-autoimmune-encephalomyelitis
#4
Karolina Podsiadło, Grzegorz Sulkowski, Beata Dąbrowska-Bouta, Lidia Strużyńska
Kinins are bioactive peptides which provide multiple functions, including critical regulation of the inflammatory response. Released during tissue injury, kinins potentiate the inflammation which represents a hallmark of numerous neurological disorders, including those of autoimmune origin such as multiple sclerosis (MS). In the present work, we assess the expression of B1 receptor (B1R) in rat brain during the course of experimental autoimmune encephalomyelitis (EAE) which is an animal model of MS. We apply pharmacological inhibition to investigate the role of this receptor in the development of neurological deficits and in shaping the cytokine/chemokine profile during the course of the disease...
February 3, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28148632/serum-neurofilament-is-associated-with-progression-of-brain-atrophy-and-disability-in-early-ms
#5
Jens Kuhle, Bardia Nourbakhsh, Donna Grant, Steve Morant, Christian Barro, Özgür Yaldizli, Daniel Pelletier, Gavin Giovannoni, Emmanuelle Waubant, Sharmilee Gnanapavan
OBJECTIVE: To investigate a potential effect of riluzole on serum neurofilaments (Nf) compared to placebo and the relationship between longitudinal clinical and MRI outcomes and serum Nf levels. METHODS: Serum samples were obtained from participants enrolled in a randomized double-blind trial of neuroprotection with riluzole vs placebo as an add-on to weekly interferon-β (IFN-β)-1a IM initiated 3 months after randomization. Nf measurements were performed by ELISA and electrochemiluminescence immunoassay...
February 1, 2017: Neurology
https://www.readbyqxmd.com/read/28139754/intranasal-delivery-of-a-novel-amnion-cell-secretome-prevents-neuronal-damage-and-preserves-function-in-a-mouse-multiple-sclerosis-model
#6
Reas S Khan, Kimberly Dine, Bailey Bauman, Michael Lorentsen, Lisa Lin, Helayna Brown, Leah R Hanson, Aleta L Svitak, Howard Wessel, Larry Brown, Kenneth S Shindler
The ability of a novel intranasally delivered amnion cell derived biologic to suppress inflammation, prevent neuronal damage and preserve neurologic function in the experimental autoimmune encephalomyelitis animal model of multiple sclerosis was assessed. Currently, there are no existing optic nerve treatment methods for disease or trauma that result in permanent vision loss. Demyelinating optic nerve inflammation, termed optic neuritis, induces permanent visual dysfunction due to retinal ganglion cell damage in multiple sclerosis and experimental autoimmune encephalomyelitis...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28117398/tryptophan-2-3-dioxygenase-tdo-deficiency-is-associated-with-subclinical-neuroprotection-in-a-mouse-model-of-multiple-sclerosis
#7
Tobias V Lanz, Sarah K Williams, Aleksandar Stojic, Simeon Iwantscheff, Jana K Sonner, Carl Grabitz, Simon Becker, Laura-Inés Böhler, Soumya R Mohapatra, Felix Sahm, Günter Küblbeck, Toshikazu Nakamura, Hiroshi Funakoshi, Christiane A Opitz, Wolfgang Wick, Ricarda Diem, Michael Platten
The catabolism of tryptophan to immunosuppressive and neuroactive kynurenines is a key metabolic pathway regulating immune responses and neurotoxicity. The rate-limiting step is controlled by indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO). IDO is expressed in antigen presenting cells during immune reactions, hepatic TDO regulates blood homeostasis of tryptophan and neuronal TDO influences neurogenesis. While the role of IDO has been described in multiple immunological settings, little is known about TDO's effects on the immune system...
January 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28116039/dimethyl-fumarate-induces-glutathione-recycling-by-upregulation-of-glutathione-reductase
#8
Christina Hoffmann, Michael Dietrich, Ann-Kathrin Herrmann, Teresa Schacht, Philipp Albrecht, Axel Methner
Neuronal degeneration in multiple sclerosis has been linked to oxidative stress. Dimethyl fumarate (DMF) is an effective oral therapeutic option shown to reduce disease activity and progression in patients with relapsing-remitting multiple sclerosis. DMF activates the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) leading to increased synthesis of the major cellular antioxidant glutathione (GSH) and prominent neuroprotection in vitro. We previously demonstrated that DMF is capable of raising GSH levels even when glutathione synthesis is inhibited, suggesting enhanced GSH recycling...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28112256/fsd-c10-a-fasudil-derivative-promotes-neuroregeneration-through-indirect-and-direct-mechanisms
#9
Yan-Hua Li, Chong Xie, Yuan Zhang, Xing Li, Hai-Fei Zhang, Qing Wang, Zhi Chai, Bao-Guo Xiao, Rodolfo Thome, Guang-Xian Zhang, Cun-Gen Ma
FSD-C10, a Fasudil derivative, was shown to reduce severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), through the modulation of the immune response and induction of neuroprotective molecules in the central nervous system (CNS). However, whether FSD-C10 can promote neuroregeneration remains unknown. In this study, we further analyzed the effect of FSD-C10 on neuroprotection and remyelination. FSD-C10-treated mice showed a longer, thicker and more intense MAP2 and synaptophysin positive signal in the CNS, with significantly fewer CD4(+) T cells, macrophages and microglia...
January 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28104249/il-17-signalling-in-astrocytes-promotes-glutamate-excitotoxicity-indications-for-the-link-between-inflammatory-and-neurodegenerative-events-in-multiple-sclerosis
#10
Milos Kostic, Nikola Zivkovic, Ana Cvetanovic, Ivana Stojanovic, Miodrag Colic
OBJECTIVE: Th-17 cells have been exclusively referred to inflammatory events in multiple sclerosis (MS), while their importance in the development of glutamate excitotoxicity and the consequent neurodegeneration has been a completely unexplored concept. Accordingly, the objective of our study was to assess IL-17A effect on astrocyte ability to metabolize and release glutamate, considering that astrocytes had the central role in glutamate homeostasis. METHODS: By using primary rat astrocyte cultures, astrocyte ability to uptake glutamate was estimated by the alterations of glutamate transporters (GLAST and GLT-1) expression, whereas changes in glutamine synthetase expression were used to estimate the ability to metabolize glutamate...
January 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28100738/mir-142-3p-is-a-key-regulator-of-il-1%C3%AE-dependent-synaptopathy-in-neuroinflammation
#11
Georgia Mandolesi, Francesca De Vito, Alessandra Musella, Antonietta Gentile, Silvia Bullitta, Diego Fresegna, Helena Sepman, Claudio Di Sanza, Nabila Haji, Francesco Mori, Fabio Buttari, Emerald Perlas, Maria Teresa Ciotti, Eran Hornstein, Irene Bozzoni, Carlo Presutti, Diego Centonze
: MicroRNAs (miRNA) play an important role in post-transcriptional gene regulation of several physiological and pathological processes. In multiple sclerosis (MS), a chronic inflammatory and degenerative disease of the CNS, and in its mouse model, the experimental autoimmune encephalomyelitis (EAE), miRNA dysregulation has been mainly related to immune system dysfunction and white matter (WM) pathology. However, little is known about their role in gray matter pathology. Here, we explored miRNA involvement in the inflammation-driven alterations of synaptic structure and function, collectively known as synaptopathy, a neuropathological process contributing to excitotoxic neurodegeneration in MS/EAE...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28095923/nadph-oxidase-in-brain-injury-and-neurodegenerative-disorders
#12
REVIEW
Merry W Ma, Jing Wang, Quanguang Zhang, Ruimin Wang, Krishnan M Dhandapani, Ratna K Vadlamudi, Darrell W Brann
Oxidative stress is a common denominator in the pathology of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis, as well as in ischemic and traumatic brain injury. The brain is highly vulnerable to oxidative damage due to its high metabolic demand. However, therapies attempting to scavenge free radicals have shown little success. By shifting the focus to inhibit the generation of damaging free radicals, recent studies have identified NADPH oxidase as a major contributor to disease pathology...
January 17, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28088365/stem-cells-for-als-an-overview-of-possible-therapeutic-approaches
#13
REVIEW
Joanna Czarzasta, Aleksandra Habich, Tomasz Siwek, Adam Czapliński, Wojciech Maksymowicz, Joanna Wojtkiewicz
Amyotrophic lateral sclerosis (ALS) is an unusual, fatal, neurodegenerative disorder leading to the loss of motor neurons. After diagnosis, the average lifespan ranges from 3 to 5 years, and death usually results from respiratory failure. Although the pathogenesis of ALS remains unclear, multiple factors are thought to contribute to the progression of ALS, such as network interactions between genes, environmental exposure, impaired molecular pathways and many others. The neuroprotective properties of neural stem cells (NSCs) and the paracrine signaling of mesenchymal stem cells (MSCs) have been examined in multiple pre-clinical trials of ALS with promising results...
January 11, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28086912/wwl70-attenuates-pge2-production-derived-from-2-arachidonoylglycerol-in-microglia-by-abhd6-independent-mechanism
#14
Mikiei Tanaka, Sean Moran, Jie Wen, Kwame Affram, Tinghua Chen, Aviva J Symes, Yumin Zhang
BACKGROUND: α/β-Hydrolase domain 6 (ABHD6) is one of the major enzymes for endocannabinoid 2-arachidonoylglycerol (2-AG) hydrolysis in microglia cells. Our recent studies have shown that a selective ABHD6 inhibitor WWL70 has anti-inflammatory and neuroprotective effects in animal models of traumatic brain injury and multiple sclerosis. However, the role of ABHD6 in the neuroinflammatory response and the mechanisms by which WWL70 suppresses inflammation has not yet been elucidated in reactive microglia...
January 10, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28069926/creatine-enhances-mitochondrial-mediated-oligodendrocyte-survival-after-demyelinating-injury
#15
Kelly A Chamberlain, Kristen S Chapey, Sonia E Nanescu, Jeffrey K Huang
Chronic oligodendrocyte loss, which occurs in the demyelinating disorder multiple sclerosis (MS), contributes to axonal dysfunction and neurodegeneration. Current therapies are able to reduce MS severity, but do not prevent transition into the progressive phase of the disease, which is characterized by chronic neurodegeneration. Therefore, pharmacological compounds that promote oligodendrocyte survival could be beneficial for neuroprotection in MS. Here, we investigated the role of creatine, an organic acid involved in adenosine triphosphate (ATP) buffering, in oligodendrocyte function...
February 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28054340/fingolimod-confers-neuroprotection-through-activation-of-rac1-after-experimental-germinal-matrix-hemorrhage-in-rat-pups
#16
William B Rolland, Paul R Krafft, Tim Lekic, Damon Klebe, Julia LeGrand, Abby Jones Weldon, Liang Xu, John H Zhang
Fingolimod, a sphingosine-1-phosphate receptor (S1PR) agonist, is clinically available to treat multiple sclerosis and is showing promise in treating stroke. We investigated if fingolimod provides long-term protection from experimental neonatal germinal matrix hemorrhage (GMH), aiming to support a potential mechanism of acute fingolimod-induced protection. GMH was induced in P7 rats by infusion of collagenase (0.3 U) into the right ganglionic eminence. Animals killed at 4 weeks post-GMH received low- or high-dose fingolimod (0...
March 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28017129/kynurenine-system-and-multiple-sclerosis-pathomechanism-and-drug-targets-with-an-emphasis-on-laquinimod
#17
Zsófia Majláth, Ádám Annus, László Vécsei
Multiple sclerosis is a common chronic, disabling autoimmune neurological disease affecting mainly young adults. In its pathomechanism, neurodegenerative and acute inflammatory characteristics are both involved. Disease-modifying therapies aim to reduce relapse-rate and slow down the deterioration in neurological functions. The currently available therapies fail to exert neuroprotective effects and most of them are associated with potentially toxic side-effects, therefore, ongoing research aims to develop novel drug candidates to cover these therapeutic gaps...
December 23, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27990061/epobis-is-a-nonerythropoietic-and-neuroprotective-agonist-of-the-erythropoietin-receptor-with-anti-inflammatory-and-memory-enhancing-effects
#18
Oksana Dmytriyeva, Stanislava Pankratova, Irina Korshunova, Peter S Walmod
The cytokine erythropoietin (EPO) stimulates proliferation and differentiation of erythroid progenitor cells. Moreover, EPO has neuroprotective, anti-inflammatory, and antioxidative effects, but the use of EPO as a neuroprotective agent is hampered by its erythropoietic activity. We have recently designed the synthetic, dendrimeric peptide, Epobis, derived from the sequence of human EPO. This peptide binds the EPO receptor and promotes neuritogenesis and neuronal cell survival. Here we demonstrate that Epobis in vitro promotes neuritogenesis in primary motoneurons and has anti-inflammatory effects as demonstrated by its ability to decrease TNF release from activated AMJ2-C8 macrophages and rat primary microglia...
2016: Mediators of Inflammation
https://www.readbyqxmd.com/read/27981909/multiple-sclerosis-and-neuroinflammation-the-overview-of-current-and-prospective-therapies
#19
Ivana Bjelobaba, Danijela Savic, Irena Lavrnja
Persistent neuroinflammation is now recognized as a chief pathological component of practically all neurodegenerative diseases. Neuroinflammation in the central nervous system (CNS), is accompanied with immune responses of glial cells. Glial cells respond to pathological stimuli through antigen presentation, and cytokine and chemokine signaling. Therefore, limiting CNS inflammation represents prospective therapeutic approach in diseases like Alzheimer's, amyotrophic lateral sclerosis, Parkinson's, ischemia, various psychiatric disorders and Multiple sclerosis (MS)...
December 14, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27923201/synthesis-and-biological-evaluation-of-a-new-class-of-benzothiazines-as-neuroprotective-agents
#20
Alessandra Mancini, Alessia Chelini, Angela Di Capua, Loretta Castelli, Simone Brogi, Marco Paolino, Germano Giuliani, Andrea Cappelli, Maria Frosini, Lorenzo Ricci, Erminia Leonelli, Gianluca Giorgi, Antonio Giordani, Jacopo Magistretti, Maurizio Anzini
Neurodegenerative diseases are disorders related to the degeneration of central neurons that gradually lead to various, severe alterations of cognitive and/or motor functions. Currently, for no such diseases does any pharmacological treatment exist able to arrest its progression. Riluzole (1) is a small molecule able to interfere with multiple cellular and molecular mechanisms of neurodegeneration, and is the only approved treatment of amyotrophic lateral sclerosis (ALS), the progression of which proved to significantly slow, thus increasing somewhat average survival...
January 27, 2017: European Journal of Medicinal Chemistry
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