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https://www.readbyqxmd.com/read/29648581/multiple-sclerosis-lesions-affect-intrinsic-functional-connectivity-of-the-spinal-cord
#1
Benjamin N Conrad, Robert L Barry, Baxter P Rogers, Satoshi Maki, Arabinda Mishra, Saakshi Thukral, Subramaniam Sriram, Aashim Bhatia, Siddharama Pawate, John C Gore, Seth A Smith
Patients with multiple sclerosis present with focal lesions throughout the spinal cord. There is a clinical need for non-invasive measurements of spinal cord activity and functional organization in multiple sclerosis, given the cord's critical role in the disease. Recent reports of spontaneous blood oxygenation level-dependent fluctuations in the spinal cord using functional MRI suggest that, like the brain, cord activity at rest is organized into distinct, synchronized functional networks among grey matter regions, likely related to motor and sensory systems...
April 10, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29614113/searching-for-neurodegeneration-in-multiple-sclerosis-at-clinical-onset-diagnostic-value-of-biomarkers
#2
Lenka Novakova, Markus Axelsson, Clas Malmeström, Henrik Imberg, Olle Elias, Henrik Zetterberg, Olle Nerman, Jan Lycke
BACKGROUND: Neurodegeneration occurs during the early stages of multiple sclerosis. It is an essential, devastating part of the pathophysiology. Tools for measuring the degree of neurodegeneration could improve diagnostics and patient characterization. OBJECTIVE: This study aimed to determine the diagnostic value of biomarkers of degeneration in patients with recent clinical onset of suspected multiple sclerosis, and to evaluate these biomarkers for characterizing disease course...
2018: PloS One
https://www.readbyqxmd.com/read/29605155/als-genes-in-the-genomic-era-and-their-implications-for-ftd
#3
REVIEW
Hung Phuoc Nguyen, Christine Van Broeckhoven, Julie van der Zee
Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease, characterized genetically by a disproportionately large contribution of rare genetic variation. Driven by advances in massive parallel sequencing and applied on large patient-control cohorts, systematic identification of these rare variants that make up the genetic architecture of ALS became feasible. In this review paper, we present a comprehensive overview of recently proposed ALS genes that were identified based on rare genetic variants (TBK1, CHCHD10, TUBA4A, CCNF, MATR3, NEK1, C21orf2, ANXA11, TIA1) and their potential relevance to frontotemporal dementia genetic etiology...
March 28, 2018: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/29598831/smoking-under-hypoxic-conditions-a-potent-environmental-risk-factor-for-inflammatory-and-autoimmune-diseases
#4
REVIEW
Md Saddam Hussain, Vishwas Tripathi
Autoimmune disease management presents a significant challenge to medical science. Environmental factors potentially increase the risk of developing inflammatory and autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and lupus. Among various environmental stresses, cigarette smoke and hypoxia have both been reported to lead to an enhanced risk of inflammatory and autoimmune diseases.In this review, we shed light on all reported mechanisms whereby cigarette smoke and a hypoxic environment can induce inflammatory and autoimmune diseases and discuss how hypoxic conditions influence the cigarette smoke-induced threat of inflammatory and autoimmune disease development...
March 30, 2018: Military Medical Research
https://www.readbyqxmd.com/read/29574826/antibody-repertoire-analysis-in-polygenic-autoimmune-diseases
#5
REVIEW
Rachael J M Bashford-Rogers, Kenneth G C Smith, David C Thomas
High-throughput sequencing of the DNA/RNA encoding antibody heavy and light chains is rapidly transforming the field of adaptive immunity. It can address key questions including (i) how the B-cell repertoire differs in health and disease and (ii) if it does differ, the point(s) in B-cell development at which this occurs. The advent of technologies, such as whole genome sequencing, offers the chance to link abnormalities in the B-cell antibody repertoire to specific genomic variants and polymorphisms. Here, we discuss the current research using B-cell antibody repertoire sequencing in three polygenic autoimmune diseases where there is good evidence for a pathological role for B-cells, namely systemic lupus erythematosus, multiple sclerosis and rheumatoid arthritis...
March 25, 2018: Immunology
https://www.readbyqxmd.com/read/29572810/chloroquine-treated-dendritic-cells-require-stat1-signaling-for-their-tolerogenic-activity
#6
Rodolfo Thome, Amanda Pires Bonfanti, Javad Rasouli, Elisabeth Rose Mari, Guang-Xian Zhang, Abdolmohamad Rostami, Liana Verinaud
Multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) are T cell-driven autoimmune diseases of the central nervous system (CNS) where interleukin (IL)-17-producing Th17 cells promote damage and are pathogenic. Conversely, tolerogenic dendritic cells (DCs) induce regulatory T (Treg) cells and suppress Th17 cells. Chloroquine (CQ) suppresses EAE through the modulation of DCs by unknown mechanisms. Here we show that signal transducer and activator of transcription (STAT) 1 is necessary for CQ-induced tolerogenic DCs (tolDCs) to efficiently suppress EAE...
March 23, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29542376/serum-neurofilament-light-chain-is-a-biomarker-of-acute-and-chronic-neuronal-damage-in-early-multiple-sclerosis
#7
Nelly Siller, Jens Kuhle, Muthuraman Muthuraman, Christian Barro, Timo Uphaus, Sergiu Groppa, Ludwig Kappos, Frauke Zipp, Stefan Bittner
BACKGROUND: Monitoring neuronal injury remains one key challenge in early relapsing-remitting multiple sclerosis (RRMS) patients. Upon axonal damage, neurofilament - a major component of the neuro-axonal cytoskeleton - is released into the cerebrospinal fluid (CSF) and subsequently peripheral blood. OBJECTIVE: To investigate the relevance of serum neurofilament light chain (sNfL) for acute and chronic axonal damage in early RRMS. METHODS: sNfL levels were determined in 74 patients (63 therapy-naive) with recently diagnosed clinically isolated syndrome (CIS) or RRMS using Single Molecule Array technology...
March 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29522453/genetic-determinants-of-antibody-levels-in-cerebrospinal-fluid-in-multiple-sclerosis-possible-links-to-endogenous-retroviruses
#8
Alexander Emmer, Christine Brütting, Malte Kornhuber, Martin S Staege
The pathogenesis of multiple sclerosis (MS) has not been clarified. In addition to environmental factors; genetic determinants have been implicated in the pathogenesis of MS. Furthermore, endogenous retroviruses (ERV) might play a role in MS. The presence of oligoclonal immunoglobulin in cerebrospinal fluid (CSF) is a typical feature of MS. Recently, genetic polymorphisms in loci on human chromosomes 6, 14 and 18 have been identified as major determinants of CSF antibody levels in MS. The functional relevance of these single nucleotide polymorphisms (SNPs) remains unclear and none of them is located in an open reading frame...
March 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29518260/inflammatory-intrathecal-profiles-and-cortical-damage-in-multiple-sclerosis
#9
R Magliozzi, O W Howell, R Nicholas, C Cruciani, M Castellaro, C Romualdi, S Rossi, M Pitteri, M D Benedetti, A Gajofatto, F B Pizzini, S Montemezzi, S Rasia, R Capra, A Bertoldo, F Facchiano, S Monaco, R Reynolds, M Calabrese
OBJECTIVE: Grey matter (GM) damage and meningeal inflammation have been associated with early disease onset and a more aggressive disease course in Multiple Sclerosis (MS), but can these changes be identified in the patient early in the disease course? METHODS: To identify possible biomarkers linking meningeal inflammation, GM damage and disease severity, gene and protein expression were analysed in meninges and CSF from 27 post-mortem secondary progressive MS (SPMS) and 14 control cases...
March 8, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29517899/photochemical-control-of-protein-arginine-deiminase-pad-activity
#10
Santanu Mondal, Sangram S Parelkar, Mitesh Nagar, Paul R Thompson
Protein Arginine deiminases (PADs) play an important role in the pathogenesis of various diseases, including rheumatoid arthritis, multiple sclerosis, lupus, ulcerative colitis and breast cancer. Therefore, the development of PAD-inhibitors has drawn significant research interest in recent years. Herein, we describe the development of the first photoswitchable PAD-inhibitors. These compounds possess an azobenzene photoswitch to optically control PAD activity. Screening of a series of inhibitors structurally similar to BB-Cl-Amidine afforded compounds 1 and 2 as the most promising candidates for the light-controlled inhibition of PAD2; the cis-isomer of 1 is 10-fold more potent than its trans-isomer, whereas the trans-isomer of 2 is 45-fold more potent than the corresponding cis-isomer...
March 8, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29515547/human-endogenous-retroviruses-and-their-putative-role-in-the-development-of-autoimmune-disorders-such-as-multiple-sclerosis
#11
REVIEW
Victoria Gröger, Holger Cynis
Human endogenous retroviruses (HERVs) are remnants of retroviral germ line infections of human ancestors and make up ~8% of the human genome. Under physiological conditions, these elements are frequently inactive or non-functional due to deactivating mutations and epigenetic control. However, they can be reactivated under certain pathological conditions and produce viral transcripts and proteins. Several disorders, like multiple sclerosis or amyotrophic lateral sclerosis are associated with increased HERV expression...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29492266/why-monkeys-do-not-get-multiple-sclerosis-spontaneously-an-evolutionary-approach
#12
REVIEW
Riley M Bove
The goal of this review is to apply an evolutionary lens to understanding the origins of multiple sclerosis (MS), integrating three broad observations. First, only humans are known to develop MS spontaneously. Second, humans have evolved large brains, with characteristically large amounts of metabolically costly myelin. This myelin is generated over long periods of neurologic development-and peak MS onset coincides with the end of myelination. Third, over the past century there has been a disproportionate increase in the rate of MS in young women of childbearing age, paralleling increasing westernization and urbanization, indicating sexually specific susceptibility in response to changing exposures...
2018: Evolution, Medicine, and Public Health
https://www.readbyqxmd.com/read/29486010/the-cellular-uptake-of-angiogenin-an-angiogenic-and-neurotrophic-factor-is-through-multiple-pathways-and-largely-dynamin-independent
#13
Ross Ferguson, Vasanta Subramanian
Angiogenin (ANG), a member of the RNase superfamily (also known as RNase 5) has neurotrophic, neuroprotective and angiogenic activities. Recently it has also been shown to be important in stem cell homeostasis. Mutations in ANG are associated with neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS) and Fronto-temporal dementia (FTD). ANG is a secreted protein which is taken up by cells and translocated to the nucleus. However, the import pathway/s through which ANG is taken up is/are still largely unclear...
2018: PloS One
https://www.readbyqxmd.com/read/29471880/-18-f-fspg-pet-reveals-increased-cystine-glutamate-antiporter-xc-activity-in-a-mouse-model-of-multiple-sclerosis
#14
Aileen Hoehne, Michelle L James, Israt S Alam, John A Ronald, Bernadette Schneider, Aloma D'Souza, Timothy H Witney, Lauren E Andrews, Haley C Cropper, Deepak Behera, Gayatri Gowrishankar, Zhaoqing Ding, Tony Wyss-Coray, Frederick T Chin, Sandip Biswal, Sanjiv S Gambhir
BACKGROUND: The cystine/glutamate antiporter (xc-) has been implicated in several neurological disorders and, specifically, in multiple sclerosis (MS) as a mediator of glutamate excitotoxicity and proinflammatory immune responses. We aimed to evaluate an xc-specific positron emission tomography (PET) radiotracer, (4S)-4-(3-[18 F]fluoropropyl)-L-glutamate ([18 F]FSPG), for its ability to allow non-invasive monitoring of xc- activity in a mouse model of MS. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice by subcutaneous injection of myelin oligodendrocyte glycoprotein (MOG35-55 ) peptide in complete Freund's adjuvant (CFA) followed by pertussis toxin...
February 22, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29464981/multiple-sclerosis-related-fatigue-altered-resting-state-functional-connectivity-of-the-ventral-striatum-and-dorsolateral-prefrontal-cortex
#15
Sven Jaeger, Friedemann Paul, Michael Scheel, Alexander Brandt, Josephine Heine, Daniel Pach, Claudia M Witt, Judith Bellmann-Strobl, Carsten Finke
OBJECTIVE: Since recent studies suggested a role of the striatum and prefrontal cortex for multiple sclerosis (MS)-related fatigue, we investigated resting-state functional connectivity alterations of striatal subdivisions and the dorsolateral prefrontal cortex (dlPFC). METHODS: Resting-state functional magnetic resonance imaging was acquired in 77 relapsing-remitting MS patients (38 fatigued (F-MS), 39 non-fatigued (NF-MS)) and 41 matched healthy controls (HC)...
February 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29455184/csf-free-light-chain-identification-of-demyelinating-disease-comparison-with-oligoclonal-banding-and-other-csf-indexes
#16
Kari M Gurtner, Eslam Shosha, Sandra C Bryant, Bruna D Andreguetto, David L Murray, Sean J Pittock, Maria Alice V Willrich
BACKGROUND: Cerebrospinal fluid (CSF) used in immunoglobulin gamma (IgG) index testing and oligoclonal bands (OCBs) are common laboratory tests used in the diagnosis of multiple sclerosis. The measurement of CSF free light chains (FLC) could pose as an alternative to the labor-intensive isoelectric-focusing (IEF) gels used for OCBs. METHODS: A total of 325 residual paired CSF and serum specimens were obtained after physician-ordered OCB IEF testing. CSF kappa (cKFLC) and lambda FLC (cLFLC), albumin and total IgG were measured...
February 19, 2018: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/29452342/neurofilament-light-chain-and-oligoclonal-bands-are-prognostic-biomarkers-in-radiologically-isolated-syndrome
#17
Clara Matute-Blanch, Luisa M Villar, José C Álvarez-Cermeño, Konrad Rejdak, Evgeniy Evdoshenko, Gleb Makshakov, Vladimir Nazarov, Sergey Lapin, Luciana Midaglia, Angela Vidal-Jordana, Jelena Drulovic, Antonio García-Merino, Antonio J Sánchez-López, Eva Havrdova, Albert Saiz, Sara Llufriu, Roberto Alvarez-Lafuente, Ina Schroeder, Uwe K Zettl, Daniela Galimberti, Lluís Ramió-Torrentà, René Robles, Ester Quintana, Harald Hegen, Florian Deisenhammer, Jordi Río, Mar Tintoré, Alex Sánchez, Xavier Montalban, Manuel Comabella
The prognostic role of cerebrospinal fluid molecular biomarkers determined in early pathogenic stages of multiple sclerosis has yet to be defined. In the present study, we aimed to investigate the prognostic value of chitinase 3 like 1 (CHI3L1), neurofilament light chain, and oligoclonal bands for conversion to clinically isolated syndrome and to multiple sclerosis in 75 patients with radiologically isolated syndrome. Cerebrospinal fluid levels of CHI3L1 and neurofilament light chain were measured by enzyme-linked immunosorbent assay...
February 14, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29438265/keep-your-eyes-wide-open-on-visual-and-vision-related-measurements-to-better-understand-multiple-sclerosis-pathophysiology
#18
Yael Backner, Netta Levin
BACKGROUND: Multiple sclerosis (MS), a demyelinating disease of the central nervous system, is multifaceted. It manifests as acute episodes as well as an accumulative chronic disability; myelin involvement as well as axonal damage; local as well as global effects; and disease load elements as well as compensatory mechanisms. The visual system, with its clear structural organization and relatively direct reflection of damage, may serve as an appropriate model to study MS. METHODS: In recent years, we have witnessed a blossoming in the field of visual measures in MS...
March 2018: Journal of Neuro-ophthalmology: the Official Journal of the North American Neuro-Ophthalmology Society
https://www.readbyqxmd.com/read/29428682/counting-of-peripheral-extracellular-vesicles-in-multiple-sclerosis-patients-by-an-improved-nanoplasmonic-assay-and-dynamic-light-scattering
#19
Antonia Mallardi, Nicoletta Nuzziello, Maria Liguori, Carlo Avolio, Gerardo Palazzo
Extracellular vesicles (EVs) are vesicles naturally secreted by the majority of human cells. Being composed by a closed phospholipid bilayer secluding proteins and RNAs they are used to transfer molecular information to other cells, thereby influencing the recipient cell functions. Despite the increasingly recognized relevance of EVs, the clarification of their physiological role is hampered by the lack of suitable analytical tools for their quantification and characterization. In this study, we have implemented a nanoplasmonic assay, previously proposed for the purity of the EV fractions, to achieve a robust analytical protocol in order to quantify the total phospholipid concentration (CPL) and the EVs number...
February 5, 2018: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29408796/search-for-new-biomarkers-of-pediatric-multiple-sclerosis-application-of-immunoglobulin-free-light-chain-analysis
#20
Esther Ganelin-Cohen, Sizilia Golderman, Regina Yeskaraev, Ayal Rozenberg, Avi Livneh, Batia Kaplan
BACKGROUND: Identifying new biomarkers is needed to overcome the diagnostic difficulties of pediatric multiple sclerosis (MS). Recently, we developed a new technique including CSF analysis of free light chain (FLC) monomers and dimers, which can improve diagnosis of adult MS. The present study has been designed to evaluate the utility of our technique for MS diagnosis in children. METHODS: Patients with MS (n=21) and non-MS demyelinating or inflammatory neurological disorders (n=35) participated in the study...
February 6, 2018: Clinical Chemistry and Laboratory Medicine: CCLM
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