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Multiple sclerosis molecular mechanism

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https://www.readbyqxmd.com/read/28915963/hepcidin-and-metallothioneins-as-molecular-base-for-sex-dependent-differences-in-clinical-course-of-experimental-autoimmune-encephalomyelitis-in-chronic-iron-overload
#1
Božena Ćurko-Cofek, Tanja Grubić Kezele, Vesna Barac-Latas
Multiple sclerosis is a chronic demyelinating disease of the central nervous system characterised by inflammatory and degenerative changes. It is considered that disease arises from the influence of environmental factors on genetically susceptible individuals. Recent researches, using magnetic resonance imaging, connected iron deposits in different brain regions with demyelinating process in multiple sclerosis patients. Although iron is an essential trace element important for many biological functions it could be harmful because iron excess can induce the production of reactive oxygen species, development of oxidative stress and lipid peroxidation which leads to demyelination...
September 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28904554/plants-derived-neuroprotective-agents-cutting-the-cycle-of-cell-death-through-multiple-mechanisms
#2
REVIEW
Taiwo Olayemi Elufioye, Tomayo Ireti Berida, Solomon Habtemariam
Neuroprotection is the preservation of the structure and function of neurons from insults arising from cellular injuries induced by a variety of agents or neurodegenerative diseases (NDs). The various NDs including Alzheimer's, Parkinson's, and Huntington's diseases as well as amyotropic lateral sclerosis affect millions of people around the world with the main risk factor being advancing age. Each of these diseases affects specific neurons and/or regions in the brain and involves characteristic pathological and molecular features...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28899915/conditional-deletion-of-the-l-type-calcium-channel-cav1-2-in-ng2-positive-cells-impairs-remyelination-in-mice
#3
Diara A Santiago González, Veronica T Cheli, Norma N Zamora, Tenzing N Lama, Vilma Spreuer, Geoffrey G Murphy, Pablo M Paez
Exploring the molecular mechanisms that drive the maturation of oligodendrocyte progenitor cells (OPCs) during the remyelination process is essential to develop new therapeutic tools to intervene in demyelinating diseases such as Multiple Sclerosis. To determine whether L-type voltage-gated calcium channels (L-VGCCs) are required for OPC development during remyelination, we have generated an inducible conditional knockout mouse in which the L-VGCC isoform Cav1.2 was deleted in NG2 positive OPCs (Cav1.2(KO))...
September 12, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28899203/an-overview-of-the-advantages-of-keap1-nrf2-system-activation-during-inflammatory-disease-treatment
#4
Nadine Keleku-Lukwete, Mikiko Suzuki, Masayuki Yamamoto
Inflammation can be defined as a protective immune response against harmful exogenous and endogenous stimuli. Nevertheless, prolonged or autoimmune inflammatory response are likely to cause pathological states associated with a production of inflammation-associated molecules along with ROS (reactive oxygen species). KEAP1-NRF2 (Kelch-like ECH-associated protein 1-Nuclear factor erythroid 2-related factor 2) signaling provides a cell protection mechanism against oxidative insults when endogenous stress defense mechanisms are imbalanced...
September 13, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28860970/failure-to-deliver-and-translate-new-insights-into-rna-dysregulation-in-als
#5
REVIEW
Alyssa N Coyne, Benjamin L Zaepfel, Daniela C Zarnescu
Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal neurodegenerative disease affecting both upper and lower motor neurons. The molecular mechanisms underlying disease pathogenesis remain largely unknown. Multiple genetic loci including genes involved in proteostasis and ribostasis have been linked to ALS providing key insights into the molecular mechanisms underlying disease. In particular, the identification of the RNA binding proteins TDP-43 and fused in sarcoma (FUS) as causative factors of ALS resulted in a paradigm shift centered on the study of RNA dysregulation as a major mechanism of disease...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28842429/anti-inflammatory-effects-of-hypoxic-preconditioned-human-periodontal-ligament-cells-secretome-in-an-experimental-model-of-multiple-sclerosis-a-key-role-of-il-37
#6
Sabrina Giacoppo, Soundara Rajan Thangavelu, Francesca Diomede, Placido Bramanti, Pio Conti, Oriana Trubiani, Emanuela Mazzon
Recent research has widely investigated the anti-inflammatory effects of mesenchymal stem cells and their secretory products, termed secretome, in the treatment of multiple sclerosis (MS). The present study examined the capacity of the conditioned medium (CM) collected from human periodontal ligament cells under hypoxic condition medium (H-hPDLSCs-CM) to suppress experimental autoimmune encephalomyelitis (EAE), a murine model of MS. To induce EAE, female C57BL/6 mice were immunized with myelin oligodendroglial glycoprotein peptide35-55 At the onset of symptoms, H-hPDLSCs-CM was infused via the tail vein of mice...
August 23, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28840473/dream-dependent-activation-of-astrocytes-in-amyotrophic-lateral-sclerosis
#7
Pilar Larrodé, Ana Cristina Calvo, Laura Moreno-Martínez, Miriam de la Torre, Leticia Moreno-García, Nora Molina, Tomás Castiella, Cristina Iñiguez, Luis Fernando Pascual, Francisco Javier Miana Mena, Pilar Zaragoza, Santiago Ramón Y Cajal, Rosario Osta
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of unknown origin and characterized by a relentless loss of motor neurons that causes a progressive muscle weakness until death. Among the several pathogenic mechanisms that have been related to ALS, a dysregulation of calcium-buffering proteins in motor neurons of the brain and spinal cord can make these neurons more vulnerable to disease progression. Downstream regulatory element antagonist modulator (DREAM) is a neuronal calcium-binding protein that plays multiple roles in the nucleus and cytosol...
August 24, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28831921/in-silico-studies-in-drug-research-against-neurodegenerative-diseases
#8
Farahnaz Rezaei Makhouri, Jahan B Ghasemi
Neurodegenerative diseases such as Alzheimer's disease (AD), progressive neurodegenerative forms of Huntington's disease, Parkinson's disease (PD), amyotrophic lateral sclerosis, spinal cerebellar ataxias, and spinal and bulbar muscular atrophy are described by slow and selective dysfunction and degeneration of neurons and axons in the central nervous system (CNS). Computer-aided or in silico design methods have matured into powerful tools for reducing the number of ligands that should be screened in experimental assays...
August 22, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28831252/preparation-characterization-and-transfection-efficiency-of-low-molecular-weight-polyethylenimine-based-nanoparticles-for-delivery-of-the-plasmid-encoding-cd200-gene
#9
Fatemeh Nouri, Hossein Sadeghpour, Reza Heidari, Ali Dehshahri
Various strategies have been utilized to improve both gene transfer efficiency and cell-induced toxicity of polyethylenimine (PEI), the most extensively investigated cationic polymeric vector. In this study, we sought to enhance transfection efficiency of low molecular weight PEI (LMW PEI) while maintaining its low toxicity by cross-linking LMW PEI via succinic acid linker. These modifications were designed to improve the hydrophilic-hydrophobic balance of the polymer, by enhancing the buffering capacity and maintaining low cytotoxic effects of the final conjugate...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28799485/monoclonal-antibodies-a-review
#10
Surjit Singh, Nitish Kumar, Pradeep Dwiwedi, Jaykaran Charan, Rimplejeet Kaur, Preeti Sidhu, Vinay Kumar Chugh
Over the last three decades, monoclonal antibodies (MAbs) have made a striking transformation from scientific tools to powerful human therapeutics. Muromonab CD3 a murine MAb, was first FDA approved therapeutic MAb for prevention of kidney transplant rejection. Since its approval in 1986, there has been decline in the further application and approvals until the late 1990s when the first chimeric Mab, Rituximab was approved for the treatment of low grade B cell lymphoma in 1997. With the approval by licensing authorities of chimeric, followed by humanized and then fully human monoclonal antibodies, rate of approval and monoclonal antibodies available in the market for the treatment of various diseases has increased dramatically...
August 9, 2017: Current Clinical Pharmacology
https://www.readbyqxmd.com/read/28792504/common-gene-network-signature-of-different-neurological-disorders-and-their-potential-implications-to-neuroaids
#11
Vidya Sagar, S Pilakka-Kanthikeel, Paola C Martinez, V S R Atluri, M Nair
The neurological complications of AIDS (neuroAIDS) during the infection of human immunodeficiency virus (HIV) are symptomized by non-specific, multifaceted neurological conditions and therefore, defining a specific diagnosis/treatment mechanism(s) for this neuro-complexity at the molecular level remains elusive. Using an in silico based integrated gene network analysis we discovered that HIV infection shares convergent gene networks with each of twelve neurological disorders selected in this study. Importantly, a common gene network was identified among HIV infection, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and age macular degeneration...
2017: PloS One
https://www.readbyqxmd.com/read/28791401/implications-of-white-matter-damage-in-amyotrophic-lateral-sclerosis-review
#12
Ting Zhou, Tina Khorshid Ahmad, Kiana Gozda, Jessica Truong, Jiming Kong, Michael Namaka
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, which involves the progressive degeneration of motor neurons. ALS has long been considered a disease of the grey matter; however, pathological alterations of the white matter (WM), including axonal loss, axonal demyelination and oligodendrocyte death, have been reported in patients with ALS. The present review examined motor neuron death as the primary cause of ALS and evaluated the associated WM damage that is guided by neuronal‑glial interactions...
October 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28747602/inflammation-amplifier-and-gateway-reflex-the-regulation-of-inflammation-by-neuroimmune-interaction
#13
Ikuma Nakagawa, Masaaki Murakami
  Central nervous system (CNS), which is made up of brain and spinal cord, is protected from the invasion of harmful agents, such as various pathogens, chemical products or immune cells by a special structure "Blood Brain Barrier (BBB)". BBB highly preserves the homeostasis of CNS environment. On the other hand, there are many diseases in CNS regions which is associated with infection or autoimmunity, that means there may exist the "gateway" for pathogens or immune cells to attack CNS. Until recently, the molecular mechanism of the gateway formation has not been elucidated...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28741645/inflammasome-and-autophagy-regulation-a-two-way-street
#14
Qian Sun, Jie Fan, Timothy R Billiar, Melanie J Scott
Inflammation plays a significant role in protecting hosts against pathogens. Inflammation induced by non-infectious, endogenous agents can be detrimental, and if excessive can result in organ and tissue damage. The inflammasome is a major innate immune pathway that can be activated via both exogenous pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs). Inflammasome activation involves formation and oligomerization of a protein complex including a NOD-like receptor (NLR), an adaptor protein (ASC) and procaspase-1...
July 24, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28726788/neuroprotection-by-eif2%C3%AE-chop-inhibition-and-xbp-1-activation-in-eae-optic-neuritiss
#15
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/28716266/sativex%C3%A2-effects-on-promoter-methylation-and-on-cnr1-cnr2-expression-in-peripheral-blood-mononuclear-cells-of-progressive-multiple-sclerosis-patients
#16
Massimo Santoro, Massimiliano Mirabella, Chiara De Fino, Assunta Bianco, Matteo Lucchini, Francesco Losavio, Andrea Sabino, Viviana Nociti
Multiple sclerosis (MS) is a chronic demyelinating central nervous system (CNS) disease that involve oligodendrocyte loss and failure to remyelinate damaged brain areas causing a progressive neurological disability. Studies in MS mouse model suggest that cannabinoids ameliorate symptoms as spasticity, tremor and pain reducing inflammation via cannabinoid-mediated system. The aim of our study is to investigate the changes in cannabinoid type 1 (CNR1) and 2 (CNR2) receptors mRNA expression levels and promoter methylation in peripheral blood mononuclear cells (PBMCs) of MS secondary progressive (MSS-SP) patients treated with Sativex®...
August 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28701918/striatal-transcriptome-and-interactome-analysis-of-shank3-overexpressing-mice-reveals-the-connectivity-between-shank3-and-mtorc1-signaling
#17
Yeunkum Lee, Sun Gyun Kim, Bokyoung Lee, Yinhua Zhang, Yoonhee Kim, Shinhyun Kim, Eunjoon Kim, Hyojin Kang, Kihoon Han
Mania causes symptoms of hyperactivity, impulsivity, elevated mood, reduced anxiety and decreased need for sleep, which suggests that the dysfunction of the striatum, a critical component of the brain motor and reward system, can be causally associated with mania. However, detailed molecular pathophysiology underlying the striatal dysfunction in mania remains largely unknown. In this study, we aimed to identify the molecular pathways showing alterations in the striatum of SH3 and multiple ankyrin repeat domains 3 (Shank3)-overexpressing transgenic (TG) mice that display manic-like behaviors...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28679106/macrophage-migration-inhibitory-factor-a-multifaceted-cytokine-implicated-in-multiple-neurological-diseases
#18
REVIEW
Marcel F Leyton-Jaimes, Joy Kahn, Adrian Israelson
Macrophage migration inhibitory factor (MIF) is a conserved cytokine found as a homotrimer protein. It is found in a wide spectrum of cell types in the body including neuronal and non-neuronal cells. MIF is implicated in several biological processes; chemo-attraction, cytokine activity, and receptor binding, among other functions. More recently, a chaperone-like activity has been added to its repertoire. In this review, we focus on the implication of MIF in the central nervous system and peripheries, its role in neurological disorders, and the mechanisms by which MIF is regulated...
July 2, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28676349/immunoregulatory-effect-of-mast-cells-influenced-by-microbes-in-neurodegenerative-diseases
#19
Francesco Girolamo, 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/28668384/mitochondria-in-neuroinflammation-multiple-sclerosis-ms-leber-hereditary-optic-neuropathy-lhon-and-lhon-ms
#20
REVIEW
David Bargiela, Patrick F Chinnery
Mitochondrial dysfunction is associated with neuroinflammation and neurodegeneration disease, but its role as a driver in these processes is uncertain. Understanding the pathogenesis of inherited mitochondrial disorders may help us to uncover mechanisms involved during acquired mitochondrial dysfunction. We review the mechanisms of mitochondrial dysfunction in Leber's hereditary optic neuropathy and multiple sclerosis and discuss shared clinical and molecular features in both conditions. Targeting mitochondrial pathways involved in inflammation or apoptosis may be a possible therapeutic approach in multiple sclerosis...
June 28, 2017: Neuroscience Letters
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