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Multiple sclerosis molecular mechanism

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https://www.readbyqxmd.com/read/29128334/a-map-of-human-mitochondrial-protein-interactions-linked-to-neurodegeneration-reveals-new-mechanisms-of-redox-homeostasis-and-nf-%C3%AE%C2%BAb-signaling
#1
Ramy H Malty, Hiroyuki Aoki, Ashwani Kumar, Sadhna Phanse, Shahreen Amin, Qingzhou Zhang, Zoran Minic, Florian Goebels, Gabriel Musso, Zhuoran Wu, Hosam Abou-Tok, Michael Meyer, Viktor Deineko, Sandy Kassir, Vishaldeep Sidhu, Matthew Jessulat, Nichollas E Scott, Xuejian Xiong, James Vlasblom, Bhanu Prasad, Leonard J Foster, Tiziana Alberio, Barbara Garavaglia, Haiyuan Yu, Gary D Bader, Ken Nakamura, John Parkinson, Mohan Babu
Mitochondrial protein (MP) dysfunction has been linked to neurodegenerative disorders (NDs); however, the discovery of the molecular mechanisms underlying NDs has been impeded by the limited characterization of interactions governing MP function. Here, using mass spectrometry (MS)-based analysis of 210 affinity-purified mitochondrial (mt) fractions isolated from 27 epitope-tagged human ND-linked MPs in HEK293 cells, we report a high-confidence MP network including 1,964 interactions among 772 proteins (>90% previously unreported)...
November 7, 2017: Cell Systems
https://www.readbyqxmd.com/read/29127843/ifn-%C3%AE-regulates-th17-differentiation-partly-through-the-inhibition-of-osteopontin-in-experimental-autoimmune-encephalomyelitis
#2
Qing Zhao, Wenjing Cheng, Yebin Xi, Zheyi Cao, Yunzhi Xu, Ting Wu, Chengzhen Li, Xiaoyin Niu, Guangjie Chen
Multiple sclerosis (MS) and the corresponding animal model, experimental autoimmune encephalomyelitis (EAE), are chronic neuroinflammatory autoimmune diseases. Increased activation of CD4+T cells, especially the Th1 and Th17 subsets, is thought to play a causal role in this disease. IFN-β is widely used in the treatment of MS and is found to decrease IL-17 and OPN production in MS patients and EAE mice. However, a definitive molecular mechanism has not yet been fully elucidated. In this study, we investigated the immunomodulatory effect of IFN-β on the EAE model...
November 7, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29114067/regulation-and-dysregulation-of-axon-infrastructure-by-myelinating-glia
#3
REVIEW
Simon Pan, Jonah R Chan
Axon loss and neurodegeneration constitute clinically debilitating sequelae in demyelinating diseases such as multiple sclerosis, but the underlying mechanisms of secondary degeneration are not well understood. Myelinating glia play a fundamental role in promoting the maturation of the axon cytoskeleton, regulating axon trafficking parameters, and imposing architectural rearrangements such as the nodes of Ranvier and their associated molecular domains. In the setting of demyelination, these changes may be reversed or persist as maladaptive features, leading to axon degeneration...
November 7, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29101799/s-allyl-cysteine-improves-clinical-and-neuropathological-features-of-experimental-autoimmune-encephalomyelitis-in-c57bl-6-mice
#4
Hossein Zeinali, Tourandokht Baluchnejadmojarad, Soudabeh Fallah, Mohsen Sedighi, Nariman Moradi, Mehrdad Roghani
Multiple sclerosis (MS) is a deleterious autoimmune and demyelinating disorder of the central nervous system with debilitating sensory and motor complications. There is still no definite cure for it and the main focus for its treatment mostly pivots around subsiding its severity and recurrence. Experimental autoimmune encephalomyelitis (EAE) is an established animal model of MS. S-allyl cysteine (SAC) is the active and main constituent of aged garlic extract with anti-inflammatory and neuroprotective property...
November 1, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29081603/neuroinflammation-and-als-transcriptomic-insights-into-molecular-disease-mechanisms-and-therapeutic-targets
#5
Giovanna Morello, Antonio Gianmaria Spampinato, Sebastiano Cavallaro
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting the motor nervous system. Despite the mechanism underlying motor neuron death is not yet clarified, multiple pathogenic processes have been proposed to account for ALS. Among these, inflammatory/immune responses have recently gained particular interest, although there are conflicting reports on the role of these processes in ALS pathogenesis and treatment. This apparent discrepancy may be due to the absence of an effective stratification of ALS patients into subgroups with markedly different clinical, biological, and molecular features...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/29066539/tcr-stimulated-changes-in-cell-surface-cd46-expression-generate-type-1-regulatory-t-cells
#6
Siobhan Ni Choileain, Joanne Hay, Joelle Thomas, Anna Williams, Matthieu M Vermeren, Cecile Benezech, Mario Gomez-Salazar, Owen R Hugues, Sonja Vermeren, Sarah E M Howie, Ian Dransfield, Anne L Astier
A lack of regulatory T cell function is a critical factor in the pathogenesis of autoimmune diseases, such as multiple sclerosis (MS). Ligation of the complement regulatory protein CD46 facilitates the differentiation of T helper 1 (TH1) effector cells into interleukin-10 (IL-10)-secreting type 1 regulatory T cells (Tr1 cells), and this pathway is defective in MS patients. Cleavage of the ectodomain of CD46, which contains three N-glycosylation sites and multiple O-glycosylation sites, enables CD46 to activate T cells...
October 24, 2017: Science Signaling
https://www.readbyqxmd.com/read/29066310/synapsin-i-deletion-reduces-neuronal-damage-and-ameliorates-clinical-progression-of-experimental-autoimmune-encephalomyelitis
#7
Fabrizia C Guarnieri, Serena Bellani, Latefa Yekhlef, Andrea Bergamaschi, Annamaria Finardi, Riccardo Fesce, Davide Pozzi, Elena Monzani, Eugenio F Fornasiero, Michela Matteoli, Gianvito Martino, Roberto Furlan, Stefano Taverna, Luca Muzio, Flavia Valtorta
The classical view of multiple sclerosis (MS) pathogenesis states that inflammation-mediated demyelination is responsible for neuronal damage and loss. However, recent findings show that impairment of neuronal functions and demyelination can be independent events, suggesting the coexistence of other pathogenic mechanisms. Due to the inflammatory milieu, subtle alterations in synaptic function occur, which are probably at the basis of the early cognitive decline that often precedes the neurodegenerative phases in MS patients...
October 21, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29055009/in-search-of-regulatory-circuits-that-control-the-biological-activity-of-vitamin-d
#8
REVIEW
Sylvia Christakos
Although the cytochrome P450 CYP27B1 plays a critical role in vitamin D biology, the molecular mechanisms involved in regulation of CYP27B1 have remained undefined. A new study has identified a kidney-specific control module distal to the Cyp27b1 gene that mediates the basal activity and hormonal regulation of Cyp27b1 This work provides a novel mechanism indicating differential regulation of Cyp27b1 in renal and non-renal cells and has implications for vitamin D biology in multiple sclerosis and perhaps other autoimmune diseases as well...
October 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29052243/wnt-%C3%AE-catenin-signalling-pathway-mediated-aberrant-hippocampal-neurogenesis-in-kainic-acid-induced-epilepsy
#9
Zhengyi Qu, Fang Su, Xueting Qi, Jianbo Sun, Hongcai Wang, Zhenkui Qiao, Hong Zhao, Yulan Zhu
Temporal lobe epilepsy is a chronic disorder of nerve system, mainly characterized by hippocampal sclerosis with massive neuronal loss and severe gliosis. Aberrant neurogenesis has been shown in the epileptogenesis process of temporal lobe epilepsy. However, the molecular mechanisms underlying aberrant neurogenesis remain unclear. The roles of Wnt signalling cascade have been well established in neurogenesis during multiple aspects. Here, we used kainic acid-induced rat epilepsy model to investigate whether Wnt/β-catenin signalling pathway is involved in the aberrant neurogenesis in temporal lobe epilepsy...
October 19, 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/29030863/hotair-but-not-anril-long-non-coding-rna-contributes-to-the-pathogenesis-of-multiple-sclerosis
#10
Majid Pahlevan Kakhki, Abbas Nikravesh, Zeinab Shirvani Farsani, Mohammad Ali Sahraian, Mehrdad Behmanesh
Different studies have revealed that dysregulation in gene expression is one of the main aspects of multiple sclerosis (MS) pathogenesis. Although the molecular pathways underlying the immunomodulatory role of vitamin D (VD) in MS is not completely elucidated, VD has more recently become a topic of interest in immune regulation and is widely administrated to MS patients as an immunomodulatory supplement. Long non-coding RNAs (lncRNAs) are known to play important roles in regulation of gene expression via different mechanisms...
October 14, 2017: Immunology
https://www.readbyqxmd.com/read/29021840/vaccination-and-autoimmune-diseases-is-prevention-of-adverse-health-effects-on-the-horizon
#11
REVIEW
Maria Vadalà, Dimitri Poddighe, Carmen Laurino, Beniamino Palmieri
Autoimmune diseases, including multiple sclerosis and type 1 diabetes mellitus, affect about 5% of the worldwide population. In the last decade, reports have accumulated on various autoimmune disorders, such as idiopathic thrombocytopenia purpura, myopericarditis, primary ovarian failure, and systemic lupus erythematosus (SLE), following vaccination. In this review, we discuss the possible underlying mechanisms of autoimmune reactions following vaccinations and review cases of autoimmune diseases that have been correlated with vaccination...
September 2017: EPMA Journal
https://www.readbyqxmd.com/read/28983300/human-tregs-made-antigen-specific-by-gene-modification-the-power-to-treat-autoimmunity-and-antidrug-antibodies-with-precision
#12
REVIEW
Patrick R Adair, Yong Chan Kim, Ai-Hong Zhang, Jeongheon Yoon, David W Scott
Human regulatory CD4(+) T cells (Tregs) are potent immunosuppressive lymphocytes responsible for immune tolerance and homeostasis. Since the seminal reports identifying Tregs, vast research has been channeled into understanding their genesis, signature molecular markers, mechanisms of suppression, and role in disease. This research has opened the doors for Tregs as a potential therapeutic for diseases and disorders such as multiple sclerosis, type I diabetes, transplantation, and immune responses to protein therapeutics, like factor VIII...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28955296/spinocerebellar-ataxia-type-2-clinicogenetic-aspects-mechanistic-insights-and-management-approaches
#13
REVIEW
Luis C Velázquez-Pérez, Roberto Rodríguez-Labrada, Juan Fernandez-Ruiz
Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant cerebellar ataxia that occurs as a consequence of abnormal CAG expansions in the ATXN2 gene. Progressive clinical features result from the neurodegeneration of cerebellum and extra-cerebellar structures including the pons, the basal ganglia, and the cerebral cortex. Clinical, electrophysiological, and imaging approaches have been used to characterize the natural history of the disease, allowing its classification into four distinct stages, with special emphasis on the prodromal stage, which is characterized by a plethora of motor and non-motor features...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28946394/bifidobacterium-animalis-in-combination-with-human-origin-of-lactobacillus-plantarum-ameliorate-neuroinflammation-in-experimental-model-of-multiple-sclerosis-by-altering-cd4-t-cell-subset-balance
#14
Zohre Salehipour, Dariush Haghmorad, Mojtaba Sankian, Maryam Rastin, Reza Nosratabadi, Mohammad Mehdi Soltan Dallal, Nafiseh Tabasi, Mahdieh Khazaee, Leila Roozbeh Nasiraii, Mahmoud Mahmoudi
BACKGROUND: Multiple Sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). Recent reports have shown that probiotics can induce immunomodulatory activity with promising effects in inflammatory diseases. This study was designed to reveal the molecular and cellular mechanisms underlying the effect of Lactobacillus plantarum A7, which comprises human commensal bacteria, and Bifidobacterium animalis, a potential probiotic strain, on alleviation of experimental autoimmune encephalomyelitis (EAE), an animal model of MS...
November 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28930607/transcriptomics-in-amyotrophic-lateral-sclerosis
#15
Marios G Krokidis, Panagiotis Vlamos
Amyotrophic lateral sclerosis (ALS) is an adult-onset, incurable neurodegenerative disease characterized by the selective death of upper and lowers motor neurons in the spinal cord, brainstem and motor cortex, which ultimately leads to paralysis and death within 2-3 years of onset. ALS is poorly understood, although multiple studies have been proposed to explain the pathophysiological mechanisms of the disorder. The development of microarray technology, for simultaneous analysis of the transcriptional expression of thousands of genes, has provided new possibilities to get better insights into the pathogenesis of ALS, and most important, potential new candidate targets for novel treatments...
January 1, 2018: Frontiers in Bioscience (Elite Edition)
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
#16
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
#17
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
#18
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 developing 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 generated an inducible conditional knock-out mouse in which the L-VGCC isoform Cav1.2 was deleted in NG2-positive OPCs (Cav1.2(KO))...
October 18, 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
#19
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 responses are likely to cause pathological states that are associated with a production of inflammation-associated molecules along with reactive oxygen species (ROS). Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2 (KEAP1-NRF2) signaling provides a cell protection mechanism against oxidative insults when endogenous stress defense mechanisms are imbalanced...
October 20, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28860970/failure-to-deliver-and-translate-new-insights-into-rna-dysregulation-in-als
#20
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
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