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https://www.readbyqxmd.com/read/28811143/nadph-oxidases-as-drug-targets-and-biomarkers-in-neurodegenerative-diseases-what-is-the-evidence
#1
REVIEW
Silvia Sorce, Roland Stocker, Tamara Seredenina, Rikard Holmdahl, Adriano Aguzzi, Adriano Chio, Antoine Depaulis, Freddy Heitz, Peter Olofsson, Tomas Olsson, Venceslas Duveau, Despina Sanoudou, Sara Skosgater, Antonia Vlahou, Dominique Wasquel, Karl-Heinz Krause, Vincent Jaquet
Neurodegenerative disease are frequently characterized by microglia activation and/or leukocyte infiltration in the parenchyma of the central nervous system and at the molecular level by increased oxidative modifications of proteins, lipids and nucleic acids. NADPH oxidases (NOX) emerged as a novel promising class of pharmacological targets for the treatment of neurodegeneration due to their role in oxidant generation and presumably in regulating microglia activation. The unique function of NOX is the generation of superoxide anion (O2(•-)) and hydrogen peroxide (H2O2)...
November 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28737506/microglia-and-c9orf72-in-neuroinflammation-and-als-and-frontotemporal-dementia
#2
REVIEW
Deepti Lall, Robert H Baloh
Amyotrophic lateral sclerosis (ALS) is a degenerative disorder that is characterized by loss of motor neurons and shows clinical, pathological, and genetic overlap with frontotemporal dementia (FTD). Activated microglia are a universal feature of ALS/FTD pathology; however, their role in disease pathogenesis remains incompletely understood. The recent discovery that ORF 72 on chromosome 9 (C9orf72), the gene most commonly mutated in ALS/FTD, has an important role in myeloid cells opened the possibility that altered microglial function plays an active role in disease...
September 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28476168/dioxins-and-related-environmental-contaminants-increase-tdp-43-levels
#3
Peter E A Ash, Elizabeth A Stanford, Ali Al Abdulatif, Alejandra Ramirez-Cardenas, Heather I Ballance, Samantha Boudeau, Amanda Jeh, James M Murithi, Yorghos Tripodis, George J Murphy, David H Sherr, Benjamin Wolozin
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative condition that is characterized by progressive loss of motor neurons and the accumulation of aggregated TAR DNA Binding Protein-43 (TDP-43, gene: TARDBP). Increasing evidence indicates that environmental factors contribute to the risk of ALS. Dioxins, related planar polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs) are environmental contaminants that activate the aryl hydrocarbon receptor (AHR), a ligand-activated, PAS family transcription factor...
May 5, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28105588/nogo-a-antibodies-for-progressive-multiple-sclerosis
#4
Benjamin V Ineichen, Patricia S Plattner, Nicolas Good, Roland Martin, Michael Linnebank, Martin E Schwab
Most of the current therapies, as well as many of the clinical trials, for multiple sclerosis (MS) target the inflammatory autoimmune processes, but less than 20% of all clinical trials investigate potential therapies for the chronic progressive disease stage of MS. The latter is responsible for the steadily increasing disability in many patients, and there is an urgent need for novel therapies that protect nervous system tissue and enhance axonal growth and/or remyelination. As outlined in this review, solid pre-clinical data suggest neutralization of the neurite outgrowth inhibitor Nogo-A as a potential new way to achieve both axonal and myelin repair...
March 2017: CNS Drugs
https://www.readbyqxmd.com/read/28097204/genomics-implicates-adaptive-and-innate-immunity-in-alzheimer-s-and-parkinson-s-diseases
#5
Sarah A Gagliano, Jennie G Pouget, John Hardy, Jo Knight, Michael R Barnes, Mina Ryten, Michael E Weale
OBJECTIVES: We assessed the current genetic evidence for the involvement of various cell types and tissue types in the etiology of neurodegenerative diseases, especially in relation to the neuroinflammatory hypothesis of neurodegenerative diseases. METHODS: We obtained large-scale genome-wide association study (GWAS) summary statistics from Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). We used multiple sclerosis (MS), an autoimmune disease of the central nervous system, as a positive control...
December 2016: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/27913903/amyotrophic-lateral-sclerosis-and-myasthenia-gravis-association-or-chance-occurrence
#6
Silvia de Pasqua, Francesco Cavallieri, Roberto D'Angelo, Fabrizio Salvi, Nicola Fini, Roberto D'Alessandro, Rita Rinaldi, Antonio Fasano, Jessica Mandrioli
Very few cases of patients with myasthenia gravis (MG) who later developed amyotrophic lateral sclerosis (ALS) have been described, although some studies showed that significantly more cases than expected have ALS associated with a prior diagnosis of autoimmune diseases. Our aim was to investigate whether the association of ALS and MG was higher than expected in a population-based study and to describe the clinical features characterizing these patients. In Emilia Romagna Region of Italy, a prospective registry has been collecting all incident ALS cases since 1...
March 2017: Neurological Sciences
https://www.readbyqxmd.com/read/27881068/neuron-microglia-interactions-in-motor-neuron-degeneration-the-inflammatory-hypothesis-in-amyotrophic-lateral-sclerosis-revisited
#7
REVIEW
Manuel J Rodríguez, Nicole Mahy
Research onto the pathogenesis of amyotrophic lateral sclerosis (ALS) has obtained notable gene discoveries, although, to date, only progress with regard to treatment has been very modest. Currently ALS is considered a multifactorial disease that presents diverse clinical presentations, ranging from a monogenic inherited disease to an autoimmune pathology, and develops with misfolded protein aggregation and neuroinflammation. An important factor related to ALS pathogenesis is the microglial activation associated with degenerative motor neurons...
2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27723283/increased-incidence-of-amyotrophic-lateral-sclerosis-in-polymyositis-a-nationwide-cohort-study
#8
Chia-Chun Tseng, Shun-Jen Chang, Wen-Chan Tsai, Tsan-Teng Ou, Cheng-Chin Wu, Wan-Yu Sung, Ming-Chia Hsieh, Jeng-Hsien Yen
OBJECTIVE: Past studies have shown common pathologic characteristics and shared immunologic features between polymyositis (PM) and amyotrophic lateral sclerosis (ALS). To explore the potential relationship between the 2 diseases, we performed a nationwide cohort study. METHODS: We identified all newly diagnosed patients with PM from Taiwan's Registry of Catastrophic Illness Database between January 1, 1998 and December 31, 2011. Each PM patient was matched to ≤5 control patients from the National Health Insurance Research Database by sex, age, and entry date...
August 2017: Arthritis Care & Research
https://www.readbyqxmd.com/read/27683876/anti-sulfoglucuronosyl-paragloboside-antibody-a-potential-serologic-marker-of-amyotrophic-lateral-sclerosis
#9
Dongpei Li, Seigo Usuki, Brandy Quarles, Michael H Rivner, Toshio Ariga, Robert K Yu
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of upper and lower motor neurons. Although the etiology of ALS is obscure, genetic studies of familiar ALS suggest a multifactorial etiology for this condition. Similarly, there probably are multiple causes for sporadic ALS. Autoimmune-mediated motor neuron dysfunction is one proposed etiology for sporadic ALS. In the present study, anti-glycolipid antibodies including GM1, GD1b, GD3, and sulfoglucuronosyl paragloboside (SGPG) were investigated in the sera of a large number of patient samples, including 113 ALS patients and 50 healthy controls, by means of enzyme-linked immunosorbent assay with affinity parametric complex criterion evaluation and thin-layer chromatography immunooverlay (immuno-TLC)...
October 2016: ASN Neuro
https://www.readbyqxmd.com/read/27552392/what-s-in-the-literature
#10
Nicholas J Silvestri, Gil I Wolfe, David Lacomis, Mark B Bromberg
The Guillain-Barré syndrome (GBS) is one of the few neuropathies well known to the general public, in part because of its association with swine flu vaccinations in 1976. GBS has again reached the general public with its possible association with Zika virus. The virus, borne by infected Aedes aegypti mosquitos, is being linked to birth defects when pregnant women are bitten and infected. There are early reports also linking GBS to Zika infection, which could expose a wider range of infected people to the neuropathy...
September 2016: Journal of Clinical Neuromuscular Disease
https://www.readbyqxmd.com/read/27102004/unusual-association-of-amyotrophic-lateral-sclerosis-and-myasthenia-gravis-a-dysregulation-of-the-adaptive-immune-system
#11
Maria Del Mar Amador, Nadia Vandenberghe, Nawel Berhoune, Jean-Philippe Camdessanché, Sophie Gronier, Emilien Delmont, Claude Desnuelle, Pascal Cintas, Sophie Pittion, Sarah Louis, Sophie Demeret, Timothée Lenglet, Vincent Meininger, François Salachas, Pierre-François Pradat, Gaëlle Bruneteau
Myasthenia gravis is an autoimmune disorder affecting neuromuscular junctions that has been associated with a small increased risk of amyotrophic lateral sclerosis (ALS). Here, we describe a retrospective series of seven cases with a concomitant diagnosis of ALS and myasthenia gravis, collected among the 18 French reference centers for ALS in a twelve year period. After careful review, only six patients strictly met the diagnostic criteria for both ALS and myasthenia gravis. In these patients, limb onset of ALS was reported in five (83%) cases...
June 2016: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/26979938/c9orf72-ablation-causes-immune-dysregulation-characterized-by-leukocyte-expansion-autoantibody-production-and-glomerulonephropathy-in-mice
#12
Amanda Atanasio, Vilma Decman, Derek White, Meg Ramos, Burcin Ikiz, Hoi-Ching Lee, Chia-Jen Siao, Susannah Brydges, Elizabeth LaRosa, Yu Bai, Wen Fury, Patricia Burfeind, Ralica Zamfirova, Gregg Warshaw, Jamie Orengo, Adelekan Oyejide, Michael Fralish, Wojtek Auerbach, William Poueymirou, Jan Freudenberg, Guochun Gong, Brian Zambrowicz, David Valenzuela, George Yancopoulos, Andrew Murphy, Gavin Thurston, Ka-Man Venus Lai
The expansion of a hexanucleotide (GGGGCC) repeat in C9ORF72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Both the function of C9ORF72 and the mechanism by which the repeat expansion drives neuropathology are unknown. To examine whether C9ORF72 haploinsufficiency induces neurological disease, we created a C9orf72-deficient mouse line. Null mice developed a robust immune phenotype characterized by myeloid expansion, T cell activation, and increased plasma cells...
March 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/26905916/what-s-in-the-literature
#13
Nicholas J Silvestri, Gil I Wolfe, Mark Bromberg, David Lacomis
In this issue, we review clinical features associated with an elevated serum creatine kinase level found in a percentage of patients with amyotrophic lateral sclerosis (ALS). The treatment of ALS remains problematic, and issues with offerings on the internet for unregulated stem cell treatment and the movement for right-to-try experimental drugs are discussed. The last What's in the Literature? discussed information about recording from stimulating electrodes implanted in the diaphragm of ALS patients, and this issue discusses the results of a randomized trial using diaphragm pacing...
March 2016: Journal of Clinical Neuromuscular Disease
https://www.readbyqxmd.com/read/26819112/trauma-induzierter-pemphigus-eine-fallserie-von-36%C3%A2-patienten
#14
Maryam Daneshpazhooh, Mina Fatehnejad, Ziba Rahbar, Kamran Balighi, Narges Ghandi, Maryam Ghiasi, Robabeh Abedini, Vahideh Lajevardi, Cheyda Chams-Davatchi
HINTERGRUND UND ZIELE: Unter dem Begriff Pemphigus wird eine Gruppe von Autoimmunkrankheiten zusammengefasst, die durch intraepidermale akantholytische Blasen gekennzeichnet sind. Der isomorphe Reizeffekt, auch als Köbner-Phänomen (KP) bezeichnet, ist definiert als das Auftreten typischer Läsionen einer bestehenden Krankheit nach einem Trauma. Dies wird bei Pemphigus selten beobachtet. Unser Ziel war es, Patienten vorzustellen, die infolge einer Hautverletzung neue Pemphigus-Läsionen entwickelten...
February 2016: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
https://www.readbyqxmd.com/read/26798979/clinical-significance-of-cation-channel-antibodies-in-motor-neuron-disease
#15
Rachel Donaldson, Jianbo Li, Yuebing Li
INTRODUCTION: Antibodies against cation channels, including voltage-gated potassium channel (VGKC) complex, voltage-gated calcium channel (VGCC), and ganglionic acetylcholine receptor (gAChR), are detected in subgroups of autoimmune disorders, and rarely occur in motor neuron disease (MND). METHODS: This investigation was a case-control study of 28 MND patients positive for cation channel antibodies in comparison with 56 age/gender/onset/diagnostic-category-matched MND patients without such antibodies...
August 2016: Muscle & Nerve
https://www.readbyqxmd.com/read/26604027/review-of-amyotrophic-lateral-sclerosis-parkinson-s-and-alzheimer-s-diseases-helps-further-define-pathology-of-the-novel-paradigm-for-alzheimer-s-with-heavy-metals-as-primary-disease-cause
#16
REVIEW
Franco Cavaleri
Pathologies of neurological diseases are increasingly recognized to have common structural and molecular events that can fit, sometimes loosely, into a central pathological theme. A better understanding of the genetic, proteomic and metabolic similarities between three common neurodegenerative diseases - Amyotrophic Lateral Sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD) - and how these similarities relate to their unique pathological features may shed more light on the underlying pathology of each...
December 2015: Medical Hypotheses
https://www.readbyqxmd.com/read/26159164/plasma-derived-from-human-umbilical-cord-blood-modulates-mitogen-induced-proliferation-of-mononuclear-cells-isolated-from-the-peripheral-blood-of-als-patients
#17
David J Eve, Jared Ehrhart, Theresa Zesiewicz, Israt Jahan, Nicole Kuzmin-Nichols, Cyndy Davis Sanberg, Clifton Gooch, Paul R Sanberg, Svitlana Garbuzova-Davis
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by degeneration of motor neurons in the spinal cord and brain. This disease clinically manifests as gradual muscular weakness and atrophy leading to paralysis and death by respiratory failure. While multiple interdependent factors may contribute to the pathogenesis of ALS, increasing evidence shows the possible presence of autoimmune mechanisms that promote disease progression. The potential use of plasma derived from human umbilical cord blood (hUCB) as a therapeutic tool is currently in its infancy...
2016: Cell Transplantation
https://www.readbyqxmd.com/read/25914733/mesenchymal-stem-cells-in-multiple-sclerosis-translation-to-clinical-trials
#18
REVIEW
A Dulamea
Multiple sclerosis is a chronic inflammatory disease of the central nervous system, characterized by an aberrant activation of the immune system and combining demyelination with neurodegeneration. Studies on experimental models of multiple sclerosis revealed immunomodulatory and immunosuppressive properties of mesenchymal stem cells. Clinical trials using mesenchymal stem cells therapy in multiple sclerosis patients showed tolerability, safety on short term, some immunomodulatory properties reducing the Th1 proinflammatory response and the inflammatory MRI parameters...
January 2015: Journal of Medicine and Life
https://www.readbyqxmd.com/read/25875836/anti-ganglioside-antibodies-in-amyotrophic-lateral-sclerosis-revisited
#19
Katja Kollewe, Ulrich Wurster, Thomas Sinzenich, Sonja Körner, Reinhard Dengler, Bahram Mohammadi, Susanne Petri
BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder with typical onset in the 5th- 6th decade of life. The hypothesis of an autoimmune origin of ALS receives less attention today, but immunological phenomena still seem to be involved and mechanisms such as protective autoimmunity may be important. Detection of antibodies against a variety of gangliosides has been repeatedly described in ALS-patients by several authors, but widely differing frequencies and titres have been reported...
2015: PloS One
https://www.readbyqxmd.com/read/25867286/transglutaminase-6-antibodies-in-the-serum-of-patients-with-amyotrophic-lateral-sclerosis
#20
Avi Gadoth, Beatrice Nefussy, Margalit Bleiberg, Tirza Klein, Irena Artman, Vivian E Drory
IMPORTANCE: Celiac disease is an autoimmune disorder triggered by gluten in genetically predisposed individuals. Gluten sensitivity can cause neurologic manifestations, such as ataxia or neuropathy, with or without gastrointestinal symptoms. Many patients with gluten ataxia produce antibodies toward the newly identified neuronal transglutaminase 6 (TG6). Two case reports described patients initially diagnosed with amyotrophic lateral sclerosis (ALS) and ultimately with celiac disease who improved with a strict gluten-free diet...
June 2015: JAMA Neurology
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