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Multiple sclerosis molecular mechanism

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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/28716266/sativex%C3%A2-effects-on-promoter-methylation-and-on-cnr1-cnr2-expression-in-peripheral-blood-mononuclear-cells-of-progressive-multiple-sclerosis-patients
#2
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
#3
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
#4
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
#5
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/28668384/mitochondria-in-neuroinflammation-multiple-sclerosis-ms-leber-hereditary-optic-neuropathy-lhon-and-lhon-ms
#6
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
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
#7
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/28641018/three-dimensional-imaging-of-transparent-tissues-via-metal-nanoparticle-labeling
#8
Abdullah Muhammad Syed, Shrey Sindhwani, Stefan Wilhelm, Benjamin R Kingston, Dennis S W Lee, Jennifer L Gommerman, Warren C W Chan
Chemical probes are key components of the bioimaging toolbox, as they label biomolecules in cells and tissues. The new challenge in bioimaging is to design chemical probes for three-dimensional (3D) tissue imaging. In this work, we discovered that light scattering of metal nanoparticles can provide 3D imaging contrast in intact and transparent tissues. The nanoparticles can act as a template for the chemical growth of a metal layer to further enhance the scattering signal. The use of chemically grown nanoparticles in whole tissues can amplify the scattering to produce a 1...
July 13, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28621357/computational-investigation-of-the-human-sod1-mutant-cys146arg-that-directs-familial-amyotrophic-lateral-sclerosis
#9
E Srinivasan, R Rajasekaran
The genetic substitution mutation of Cys146Arg in the SOD1 protein is predominantly found in the Japanese population suffering from familial amyotrophic lateral sclerosis (FALS). A complete study of the biophysical aspects of this particular missense mutation through conformational analysis and producing free energy landscapes could provide an insight into the pathogenic mechanism of ALS disease. In this study, we utilized general molecular dynamics simulations along with computational predictions to assess the structural characterization of the protein as well as the conformational preferences of monomeric wild type and mutant SOD1...
June 16, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28579973/conflicting-role-of-mycobacterium-species-in-multiple-sclerosis
#10
REVIEW
Davide Cossu, Kazumasa Yokoyama, Nobutaka Hattori
Mycobacterium is a genus of aerobic and acid-fast bacteria, which include several pathogenic organisms that cause serious diseases in mammals. Previous studies have associated the immune response against mycobacteria with multiple sclerosis (MS), a chronic demyelinating disease of the central nervous system with unknown etiology. The role of mycobacteria in the pathological process has been controversial and often conflicting. We provide a detailed review of the mycobacteria that have been linked to MS over the last three decades, with a focus on Mycobacterium bovis bacille Calmette-Guérin vaccine for human and oral exposure to Mycobacterium avium subsp...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28576565/the-expression-of-vdr-mrna-but-not-nf-%C3%AE%C2%BAb-surprisingly-decreased-after-vitamin-d-treatment-in-multiple-sclerosis-patients
#11
Zeinab Shirvani-Farsani, Majid Pahlevan Kakhki, Bahar Naghavi Gargari, Roozita Doosti, Abdorreza Naser Moghadasi, Amir Reza Azimi, Mehrdad Behmanesh
BACKGROUND AND PURPOSE: The aim of this study was to investigate the expression levels of vitamin D receptor (VDR) and NF-κB mRNAs in vitamin D (VD) supplemented multiple sclerosis (MS) patients. METHODS: RRMS patients received 50,000 IU vitamin D3/week as an intra-muscular injection for 2 months. Blood samples were obtained from 30 MS patients before and after VD supplementation and 32 healthy individuals, and then VDR and NF-κB mRNA levels were measured by real time PCR method and analyzed with independent and paired t-tests...
July 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28539871/protein-quality-control-and-the-amyotrophic-lateral-sclerosis-frontotemporal-dementia-continuum
#12
Hamideh Shahheydari, Audrey Ragagnin, Adam K Walker, Reka P Toth, Marta Vidal, Cyril J Jagaraj, Emma R Perri, Anna Konopka, Jessica M Sultana, Julie D Atkin
Protein homeostasis, or proteostasis, has an important regulatory role in cellular function. Protein quality control mechanisms, including protein folding and protein degradation processes, have a crucial function in post-mitotic neurons. Cellular protein quality control relies on multiple strategies, including molecular chaperones, autophagy, the ubiquitin proteasome system, endoplasmic reticulum (ER)-associated degradation (ERAD) and the formation of stress granules (SGs), to regulate proteostasis. Neurodegenerative diseases are characterized by the presence of misfolded protein aggregates, implying that protein quality control mechanisms are dysfunctional in these conditions...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28493107/beyond-immunomodulation-the-regenerative-role-for-regulatory-t-cells-in-central-nervous-system-remyelination
#13
REVIEW
Veronique E Miron
Central nervous system regeneration after injury can occur in the form of remyelination, the reinstatement of myelin around axons which restores axon health and function. However, remyelination often fails in chronic neurological diseases, such as progressive multiple sclerosis. The lack of currently approved pro-remyelination therapies highlights the need to elucidate the cellular and molecular mechanisms underpinning this regenerative process. Whereas some T lymphocyte subsets such as Th1 and Th17 are implicated in inducing myelin injury, a recent study by Dombrowski et al...
June 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28468939/modelling-amyotrophic-lateral-sclerosis-progress-and-possibilities
#14
REVIEW
Philip Van Damme, Wim Robberecht, Ludo Van Den Bosch
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that primarily affects the motor system and presents with progressive muscle weakness. Most patients survive for only 2-5 years after disease onset, often due to failure of the respiratory muscles. ALS is a familial disease in ∼10% of patients, with the remaining 90% developing sporadic ALS. Over the past decade, major advances have been made in our understanding of the genetics and neuropathology of ALS. To date, around 20 genes are associated with ALS, with the most common causes of typical ALS associated with mutations in SOD1, TARDBP, FUS and C9orf72 Advances in our understanding of the genetic basis of ALS have led to the creation of different models of this disease...
May 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28467828/dominant-protection-from-hla-linked-autoimmunity-by-antigen-specific-regulatory-t-cells
#15
Joshua D Ooi, Jan Petersen, Yu H Tan, Megan Huynh, Zoe J Willett, Sri H Ramarathinam, Peter J Eggenhuizen, Khai L Loh, Katherine A Watson, Poh Y Gan, Maliha A Alikhan, Nadine L Dudek, Andreas Handel, Billy G Hudson, Lars Fugger, David A Power, Stephen G Holt, P Toby Coates, Jon W Gregersen, Anthony W Purcell, Stephen R Holdsworth, Nicole L La Gruta, Hugh H Reid, Jamie Rossjohn, A Richard Kitching
Susceptibility and protection against human autoimmune diseases, including type I diabetes, multiple sclerosis, and Goodpasture disease, is associated with particular human leukocyte antigen (HLA) alleles. However, the mechanisms underpinning such HLA-mediated effects on self-tolerance remain unclear. Here we investigate the molecular mechanism of Goodpasture disease, an HLA-linked autoimmune renal disorder characterized by an immunodominant CD4(+) T-cell self-epitope derived from the α3 chain of type IV collagen (α3135-145)...
May 11, 2017: Nature
https://www.readbyqxmd.com/read/28467798/mechanism-of-oxidative-stress-p38mapk-sgk1-signaling-axis-in-experimental-autoimmune-encephalomyelitis-eae
#16
Liang Wang, Bin Li, Mo-Yuan Quan, Lin Li, Yuan Chen, Guo-Jun Tan, Jing Zhang, Xiao-Peng Liu, Li Guo
BACKGROUND: Multiple sclerosis (MS), a complex disease associated with multifocal demyelination of the central nervous system and poorly understood etiology. It has been previously indicated that many factors, including oxidative stress and p38MAPK-SGK1 pathway, contribute to the pathogenesis of MS. METHODS: This study, using an experimental autoimmune encephalomyelitis (EAE) model system, was aimed at investigating the molecular mechanisms determining interaction p38MAPK-SGK1 pathway and oxidative stress in MS pathogenesis...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28459188/the-actin-cytoskeleton-in-sma-and-als-how-does-it-contribute-to-motoneuron-degeneration
#17
Niko Hensel, Peter Claus
Amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) are neurodegenerative diseases with overlapping clinical phenotypes based on impaired motoneuron function. However, the pathomechanisms of both diseases are largely unknown, and it is still unclear whether they converge on the molecular level. SMA is a monogenic disease caused by low levels of functional Survival of Motoneuron (SMN) protein, whereas ALS involves multiple genes as well as environmental factors. Recent evidence argues for involvement of actin regulation as a causative and dysregulated process in both diseases...
April 1, 2017: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
https://www.readbyqxmd.com/read/28458392/il-17-triggered-downregulation-of-mir-497-results-in-high-hif-1%C3%AE-expression-and-consequent-il-1%C3%AE-and-il-6-production-by-astrocytes-in-eae-mice
#18
Kai Shan, Rongrong Pang, Chenhui Zhao, Xiaomei Liu, Wenxing Gao, Jing Zhang, Dan Zhao, Yingwei Wang, Wen Qiu
Interleukin 17 (IL-17) is increasingly recognized as a key factor that contributes to the pathogenesis of multiple sclerosis (MS) and its experimental mouse autoimmune encephalomyelitis (EAE) model. However, the roles and regulatory mechanisms of IL-17-induced pro-inflammatory cytokine production in EAE mice remain largely unclear. In this study, the expression of IL-17, hypoxia inducible factor-1α (HIF-1α), IL-1β, IL-6 and microRNA-497 (miR-497), as well as their intrinsic associations, was investigated using EAE model mice and cultured astrocytes exposed to IL-17 in vitro...
May 1, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28445677/overexpression-of-the-cytokine-baff-and-autoimmunity-risk
#19
Maristella Steri, Valeria Orrù, M Laura Idda, Maristella Pitzalis, Mauro Pala, Ilenia Zara, Carlo Sidore, Valeria Faà, Matteo Floris, Manila Deiana, Isadora Asunis, Eleonora Porcu, Antonella Mulas, Maria G Piras, Monia Lobina, Sandra Lai, Mara Marongiu, Valentina Serra, Michele Marongiu, Gabriella Sole, Fabio Busonero, Andrea Maschio, Roberto Cusano, Gianmauro Cuccuru, Francesca Deidda, Fausto Poddie, Gabriele Farina, Mariano Dei, Francesca Virdis, Stefania Olla, Maria A Satta, Mario Pani, Alessandro Delitala, Eleonora Cocco, Jessica Frau, Giancarlo Coghe, Lorena Lorefice, Giuseppe Fenu, Paola Ferrigno, Maria Ban, Nadia Barizzone, Maurizio Leone, Franca R Guerini, Matteo Piga, Davide Firinu, Ingrid Kockum, Izaura Lima Bomfim, Tomas Olsson, Lars Alfredsson, Ana Suarez, Patricia E Carreira, Maria J Castillo-Palma, Joseph H Marcus, Mauro Congia, Andrea Angius, Maurizio Melis, Antonio Gonzalez, Marta E Alarcón Riquelme, Berta M da Silva, Maurizio Marchini, Maria G Danieli, Stefano Del Giacco, Alessandro Mathieu, Antonello Pani, Stephen B Montgomery, Giulio Rosati, Jan Hillert, Stephen Sawcer, Sandra D'Alfonso, John A Todd, John Novembre, Gonçalo R Abecasis, Michael B Whalen, Maria G Marrosu, Alessandra Meloni, Serena Sanna, Myriam Gorospe, David Schlessinger, Edoardo Fiorillo, Magdalena Zoledziewska, Francesco Cucca
BACKGROUND: Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and for even fewer have the causal variant and underlying mechanism been defined. Coincident associations of DNA variants affecting both the risk of autoimmune disease and quantitative immune variables provide an informative route to explore disease mechanisms and drug-targetable pathways...
April 27, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28440186/the-double-roles-of-the-prostaglandin-e2-ep2-receptor-in-intracerebral-hemorrhage
#20
Xu Luo, Qiquan Zhu, Jie Zhang, Qin Huang, Zongyi Xie, Yuan Cheng
Intracerebral hemorrhage (ICH), a subtype of stroke, brings high morbidity and mortality to human beings. Multiple studies indicate that neuroinflammation, excitotoxicity, oxidative stress, cytotoxicity resulted from the degradation products of blood clot play vital roles in ICH-induced secondary brain injury, which contributes to deterioration of neurological outcome. Prostaglandin E2 (PGE2), a type of prostanoids commonly up-regulated in these progresses, is known to modulate numerous cellular and molecular processes and involve in various diseases, including ICH, cerebral ischemic, Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) etc...
April 24, 2017: Current Drug Targets
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