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Neuroprotection in multiple sclerosis

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https://www.readbyqxmd.com/read/28088365/stem-cells-for-als-an-overview-of-possible-therapeutic-approaches
#1
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
#2
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-following-demyelinating-injury
#3
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 ATP buffering, in oligodendrocyte function...
January 9, 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
#4
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 euthanized at four weeks post-GMH received low or high dose fingolimod (0...
January 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28017129/kynurenine-system-and-multiple-sclerosis-pathomechanism-and-drug-targets-with-an-emphasis-on-laquinimod
#5
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
#6
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
#7
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
#8
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...
November 27, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27920149/mir-142-3p-is-a-key-regulator-of-il-1%C3%AE-dependent-synaptopathy-in-neuroinflammation
#9
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 posttranscriptional 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 pathology. However, little is known about their role in grey 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...
December 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27918427/prolactin-friend-or-foe-in-central-nervous-system-autoimmune-inflammation
#10
REVIEW
Massimo Costanza, Rosetta Pedotti
The higher prevalence of multiple sclerosis (MS) in females, along with the modulation of disease activity observed during pregnancy and the post-partum period, has suggested a hormonal influence in MS. Even if prolactin (PRL) does not belong to the sex hormones family, its crucial role in female reproduction and lactation has prompted great efforts to understand if PRL could represent a gender factor in the pathogenesis of MS and experimental autoimmune encephalomyelitis (EAE), the animal model for this disease...
December 2, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27917122/glucagon-like-peptide-1-analog-liraglutide-delays-onset-of-experimental-autoimmune-encephalitis-in-lewis-rats
#11
Brian DellaValle, Gitte S Brix, Birgitte Brock, Michael Gejl, Anne M Landau, Arne Møller, Jørgen Rungby, Agnete Larsen
Introduction: Recent findings indicate that metabolic disturbances are involved in multiple sclerosis (MS) pathology and influence the susceptibility to treatment, directing attention toward anti-diabetic drugs such as metformin and pioglitazone. Liraglutide, a drug of the glucagon-like peptide-1 (GLP-1) family, is also anti-diabetic and weight-reducing and is, moreover, directly neuroprotective and anti-inflammatory in a broad spectrum of experimental models of brain disease. In this study we investigate the potential for this FDA-approved drug, liraglutide, as a treatment for MS by utilizing the experimental model, experimental autoimmune encephalitis (EAE)...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27904492/hydroxycitric-acid-ameliorates-inflammation-and-oxidative-stress-in-mouse-models-of-multiple-sclerosis
#12
Mahdi Goudarzvand, Sanaz Afraei, Somaye Yaslianifard, Saleh Ghiasy, Ghazal Sadri, Mustafa Kalvandi, Tina Alinia, Ali Mohebbi, Reza Yazdani, Shahin Khadem Azarian, Abbas Mirshafiey, Gholamreza Azizi
Hydroxycitric acid (HCA) is derived primarily from the Garcinia plant and is widely used for its anti-inflammatory effects. Multiple sclerosis can cause an inflammatory demyelination and axonal damage. In this study, to validate the hypothesis that HCA exhibits therapeutic effects on multiple sclerosis, we established female C57BL/6 mouse models of multiple sclerosis, i.e., experimental autoimmune encephalomyelitis, using Complete Freund's Adjuvant (CFA) emulsion containing myelin oligodendrocyte glycoprotein (35-55)...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27889959/fumaric-acid-esters-attenuate-secondary-degeneration-following-spinal-cord-injury
#13
Marika Cordaro, Giovanna Casili, Irene Paterniti, Salvatore Cuzzocrea, Emanuela Esposito
Spinal cord injury (SCI) causes permanent changes in motor, sensory and autonomic functions. Unfortunately, there are not a stable cures and current treatments include surgical decompression, methylprednisolone and hemodynamic control that lead to modest function recovery. Fumaric acid esters (FAEs) were firstly used in the management of an immunological skin disorder, such as psoriasis. Because of their potent anti-inflammatory effects, they have been introduced in multiple sclerosis. Investigation shown not only anti-inflammatory, but also supposed neuroprotective mechanism of action...
November 27, 2016: Journal of Neurotrauma
https://www.readbyqxmd.com/read/27882351/activity-of-nav1-2-promotes-neurodegeneration-in-an-animal-model-of-multiple-sclerosis
#14
Benjamin Schattling, Walid Fazeli, Birgit Engeland, Yuanyuan Liu, Holger Lerche, Dirk Isbrandt, Manuel A Friese
Counteracting the progressive neurological disability caused by neuronal and axonal loss is the major unmet clinical need in multiple sclerosis therapy. However, the mechanisms underlying irreversible neuroaxonal degeneration in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE) are not well understood. A long-standing hypothesis holds that the distribution of voltage-gated sodium channels along demyelinated axons contributes to neurodegeneration by increasing neuroaxonal sodium influx and energy demand during CNS inflammation...
November 17, 2016: JCI Insight
https://www.readbyqxmd.com/read/27876534/transcranial-magnetic-stimulation-modifies-astrocytosis-cell-density-and-lipopolysaccharide-levels-in-experimental-autoimmune-encephalomyelitis
#15
Francisco J Medina-Fernández, Evelio Luque, Macarena Aguilar-Luque, Eduardo Agüera, Montserrat Feijóo, Fe I García-Maceira, Begoña M Escribano, Álvaro Pascual-Leone, René Drucker-Colín, Isaac Túnez
AIMS: Experimental autoimmune encephalomyelitis (EAE) is considered a valid experimental model for multiple sclerosis, a chronic neuroinflammatory condition of the central nervous system. Additionally, some evidence has shown that some microbial products such as the bacterial lipopolysaccharide could lead to the activation of reactive immune cells, triggering neuroinflammation. Several studies have found that transcranial magnetic stimulation (TMS) may exert a neuroprotective effect. Therefore, we aimed to assess the effect of TMS on the neuroinflammation occurring in EAE...
November 19, 2016: Life Sciences
https://www.readbyqxmd.com/read/27865736/ips-derived-neural-progenitor-cells-from-ppms-patients-reveal-defect-in-myelin-injury-response
#16
Alexandra M Nicaise, Erin Banda, Rosa M Guzzo, Kristen Russomanno, Wanda Castro-Borrero, Cory M Willis, Kasey M Johnson, Albert C Lo, Stephen J Crocker
Primary progressive multiple sclerosis (PPMS) is a chronic demyelinating disease of the central nervous system (CNS) currently lacking any effective treatment. Promoting endogenous brain repair offers a potential strategy to halt and possibly restore neurologic function in PPMS. To understand how the microenvironment within white matter lesions plays a role in repair we have focused on neural progenitor cells (NPCs) since these are found in lesions in PPMS and have been found to influence oligodendrocyte progenitor cell maturation (OPCs)...
February 2017: Experimental Neurology
https://www.readbyqxmd.com/read/27829982/new-insights-into-the-role-of-oxidative-stress-mechanisms-in-the-pathophysiology-and-treatment-of-multiple-sclerosis
#17
REVIEW
Bożena Adamczyk, Monika Adamczyk-Sowa
Multiple sclerosis (MS) is a multifactorial disease of the central nervous system (CNS) characterized by an inflammatory process and demyelination. The etiology of the disease is still not fully understood. Therefore, finding new etiological factors is of such crucial importance. It is suspected that the development of MS may be affected by oxidative stress (OS). In the acute phase OS initiates inflammatory processes and in the chronic phase it sustains neurodegeneration. Redox processes in MS are associated with mitochondrial dysfunction, dysregulation of axonal bioenergetics, iron accumulation in the brain, impaired oxidant/antioxidant balance, and OS memory...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27823573/the-sphingosine-1-phosphate-signaling-pathway-in-epilepsy-a-possible-role-for-the-immunomodulator-drug-fingolimod-in-epilepsy-treatment
#18
Antonio Leo, Rita Citraro, Rosario Marra, Ernesto Palma, Eugenio Donato Di Paola, Andrew Constanti, Giovambattista De Sarro, Emilio Russo
It is currently known that erythrocytes are the major source of sphingosine 1-phosphate (S1P) in the body. S1P acts both extracellularly as a cellular mediator and intracellularly as an important second messenger molecule. Its effects are mediated by interaction with five specific types of G protein-coupled S1P receptor. Fingolimod, is a recognized modulator of S1P receptors, and is the first orally active disease-modifying therapy that has been approved for the treatment of multiple sclerosis. Magnetic resonance imaging data suggest that fingolimod may be effective in multiple sclerosis MS by preventing blood-brain barrier disruption and brain atrophy...
November 4, 2016: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/27813441/primary-progressive-multiple-sclerosis-current-therapeutic-strategies-and-future-perspectives
#19
Alberto Gajofatto, Marco Turatti, Maria Donata Benedetti
Multiple sclerosis (MS) is a chronic inflammatory condition of the central nervous system with heterogeneous features. Primary progressive (PP) MS is a rare disease subtype characterized by continuous disability worsening from onset. No disease-modifying therapy is currently approved for PP MS due to the negative or inconsistent results of clinical trials conducted on a wide range of interventions, which are reviewed in the present paper. Areas covered: The features and results of randomized trials of disease-modifying treatments for PP MS are discussed, including immunosuppressants, immunomodulators, monoclonal antibodies, and putative neuroprotective agents...
November 4, 2016: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/27804858/heat-shock-proteins-old-and-novel-roles-in-neurodegenerative-diseases-in-the-central-nervous-system
#20
Sandra Amor, Marianna Bugiani, Johannes M van Noort
Heat shock proteins (HSPs) are families of molecular chaperones that play important homeostatic functions in the central nervous system (CNS) by preventing protein misfolding, promoting degradation of improperly folded proteins, and protecting against apoptosis and inflammatory damage especially during hyperthermia, hypoxia, or oxidative stress. Under stress conditions, HSPs are upregulated to protect cells from damage that accumulates during ageing as well as pathological conditions. An important, yet frequently overlooked function of some HSPs is their ability to function as extracellular messengers (also termed chaperokines) that modulate immune responses within the CNS...
October 31, 2016: CNS & Neurological Disorders Drug Targets
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