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Multiple sclerosis molecular mechanism

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https://www.readbyqxmd.com/read/29339071/mir-155-5p-promotes-fibroblast-cell-proliferation-and-inhibits-foxo-signaling-pathway-in-vulvar-lichen-sclerosis-by-targeting-foxo3-and-cdkn1b
#1
Lina Ren, Yi Zhao, Xiaoxi Huo, Xin Wu
Vulvar lichen sclerosis (VLS) is a chronic inflammatory skin disorder. Evidence is accumulating that microRNAs (miRNAs) exert crucial roles in initiation and development of a wide range of human diseases. MiR-155-5p has been frequently reported to be implicated in the tumorigenesis and progression of multiple types of cancers, however, its biological role in VLS remains unclear. This study aimed to explore the role of miR-155-5p in VLS and clarify the potential molecular mechanisms involved. In the present study, miR-155-5p was observed to be significantly upregulated in VLS tissues...
January 12, 2018: Gene
https://www.readbyqxmd.com/read/29331073/cerebrospinal-fluid-macrophage-biomarkers-in-amyotrophic-lateral-sclerosis
#2
A G Thompson, E Gray, M-L Thézénas, P D Charles, S Evetts, M T Hu, K Talbot, R Fischer, B M Kessler, M R Turner
Objective The neurodegenerative disease amyotrophic lateral sclerosis (ALS) is a heterogeneous clinical syndrome involving multiple molecular pathways. The development of biomarkers for use in therapeutic trials is a priority. We sought to use a high-throughput proteomic method to identify novel biomarkers in individual cerebrospinal fluid samples. Methods Liquid chromatography-tandem mass spectrometry with label-free quantification was used to identify cerebrospinal fluid proteins using samples from a well-characterised longitudinal cohort comprising patients with ALS (n=43), the upper motor neuron variant primary lateral sclerosis (PLS, n=6), cross-sectional healthy (n=20) and disease controls (Parkinsons's n=20, ALS mimic disorders n=12)...
January 13, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29290406/elevated-expression-of-granulocyte-macrophage-colony-stimulating-factor-receptor-in-multiple-sclerosis-lesions
#3
Jaime Imitola, Javad Rasouli, Fumihiro Watanabe, Kader Mahajan, Aswhini D Sharan, Bogoljub Ciric, Guang-Xian Zhang, Abdolmohamad Rostami
Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease that disproportionately affects young adults, leading to disability and high costs to society. Infiltration of T cells and monocytes into the central nervous system (CNS) is critical for disease initiation and progression. However, despite a great deal of effort the molecular mechanisms by which immune cells initiate and perpetuate CNS damage in MS have not yet been elucidated. In experimental autoimmune encephalomyelitis (EAE), an animal model of MS, granulocyte-macrophage colony-stimulating factor (GM-CSF) produced by pathogenic Th1 and Th17 cells is critical for the recruitment of monocytes into the CNS during the initial stage of disease...
December 22, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29288338/toll-like-receptor-2-mediated-glial-cell-activation-in-a-mouse-model-of-cuprizone-induced-demyelination
#4
Stefan Esser, Larissa Göpfrich, Kai Bihler, Eugenia Kress, Stella Nyamoya, Simone C Tauber, Tim Clarner, Matthias B Stope, Thomas Pufe, Markus Kipp, Lars-Ove Brandenburg
Multiple sclerosis (MS) is a chronic degenerative disease of the central nervous system that is characterized by myelin abnormalities, oligodendrocyte pathology, and concomitant glia activation. The factors triggering gliosis and demyelination are currently not well characterized. New findings suggest an important role of the innate immune response in the initiation and progression of active demyelinating lesions. Especially during progressive disease, aberrant glia activation rather than the invasion of peripheral immune cells is accountable for progressive neuronal injury...
December 29, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29279008/comparative-analysis-of-thermal-unfolding-simulations-of-rna-recognition-motifs-rrms-of-tar-dna-binding-protein-43-tdp-43
#5
Amresh Prakash, Vijay Kumar, Naveen Kumar Meena, Md Imtaiyaz Hassan, Andrew M Lynn
TAR DNA-binding protein 43 (TDP-43) inclusions have been found in Amyotrophic lateral sclerosis (ALS) and several other neurodegenerative diseases. Many studies suggest the involvement of RNA recognition motifs (RRMs) in TDP-43 proteinopathy. To elucidate the structural stability and the unfolding dynamics of RRMs, we have carried out atomistic molecular dynamics simulations at two different temperatures (300 K and 500 K). The simulations results indicate that there are distinct structural differences in the unfolding pathway between the two domains and RRM1 unfolds faster than RRM2 in accordance with the lower thermal stability found experimentally...
December 26, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29275836/a-cellular-and-molecular-view-of-t-helper-17%C3%A2-cell-plasticity-in-autoimmunity
#6
REVIEW
Ralph Stadhouders, Erik Lubberts, Rudi W Hendriks
Since the original identification of the T helper 17 (Th17) subset in 2005, it has become evident that these cells do not only contribute to host defence against pathogens, such as bacteria and fungi, but that they are also critically involved in the pathogenesis of many autoimmune diseases. In contrast to the classic Th1 and Th2 cells, which represent rather stably polarized subsets, Th17 cells display remarkable heterogeneity and plasticity. This has been attributed to the characteristics of the key transcription factor that guides Th17 differentiation, retinoic acid receptor-related orphan nuclear receptor gamma (RORγ)...
December 21, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29259705/the-roles-of-rgma-neogenin-signaling-in-inflammation-and-angiogenesis
#7
REVIEW
Yuki Fujita, Toshihide Yamashita
Repulsive guidance molecule (RGM) is a glycosylphosphatidylinositol (GPI)-anchored glycoprotein that has diverse functions in the developing and pathological central nervous system (CNS). The binding of RGM to its receptor neogenin regulates axon guidance, neuronal differentiation, and survival during the development of the CNS. In the pathological state, RGM expression is induced after spinal cord injury, and the inhibition of RGM promotes axon growth and functional recovery. Furthermore, RGM expression is also observed in immune cells, and RGM regulates inflammation and neurodegeneration in autoimmune encephalomyelitis...
2017: Inflammation and Regeneration
https://www.readbyqxmd.com/read/29246870/metabolic-defects-in-multiple-sclerosis
#8
REVIEW
Reginald C Adiele, Chiedukam A Adiele
Brain injuries in multiple sclerosis (MS) involve immunopathological, structural and metabolic defects on myelin sheath, oligodendrocytes (OLs), axons and neurons suggesting that different cellular mechanisms ultimately result in the formation of MS plaques, demyelination, inflammation and brain damage. Bioenergetics, oxygen and ion metabolism dominate the metabolic and biochemical pathways that maintain neuronal viability and impulse transmission which directly or indirectly point to mitochondrial integrity and adenosine triphosphate (ATP) availability indicating the involvement of mitochondria in the pathogenesis of MS...
December 13, 2017: Mitochondrion
https://www.readbyqxmd.com/read/29234010/loss-of-the-molecular-clock-in-myeloid-cells-exacerbates-t-cell-mediated-cns-autoimmune-disease
#9
Caroline E Sutton, Conor M Finlay, Mathilde Raverdeau, James O Early, Joseph DeCourcey, Zbigniew Zaslona, Luke A J O'Neill, Kingston H G Mills, Annie M Curtis
The transcription factor BMAL1 is a core component of the molecular clock, regulating biological pathways that drive 24 h (circadian) rhythms in behaviour and physiology. The molecular clock has a profound influence on innate immune function, and circadian disruption is linked with increased incidence of multiple sclerosis (MS). However, the mechanisms underlying this association are unknown. Here we show that BMAL1 and time-of-day regulate the accumulation and activation of various immune cells in a CNS autoimmune disease model, experimental autoimmune encephalomyelitis (EAE)...
December 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29215724/pericytes-modulate-myelination-in-the-central-nervous-system
#10
Patrick O Azevedo, Isadora F G Sena, Julia P Andreotti, Juliana Carvalho-Tavares, José C Alves-Filho, Thiago M Cunha, Fernando Q Cunha, Akiva Mintz, Alexander Birbrair
Multiple sclerosis is a highly prevalent chronic demyelinating disease of the central nervous system. Remyelination is the major therapeutic goal for this disorder. The lack of detailed knowledge about the cellular and molecular mechanisms involved in myelination restricts the design of effective treatments. De La Fuente et al. (2017) by using state-of-the-art techniques, including pericyte-deficient mice in combination with induced demyelination, reveal that pericytes participate in central nervous system regeneration...
December 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29203519/s1p1-modulator-induced-g%C3%AE-i-signaling-and-%C3%AE-arrestin-recruitment-are-both-necessary-to-induce-rapid-and-efficient-reduction-of-blood-lymphocyte-count-in-vivo
#11
Magdalena Birker-Robaczewska, Martin Bolli, Markus Rey, Ruben de Kanter, Christopher Kohl, Cyrille Lescop, Maxime Boucher, Sylvie Poirey, Beat Steiner, Oliver Nayler
S1P1 (sphingosine-1-phosphate receptor 1) agonists prevent lymphocyte egress from secondary lymphoid organs and cause a reduction of the number of circulating blood lymphocytes. We hypothesized that S1P1 receptor modulators with pathway-selective signaling properties could help to further elucidate molecular mechanisms involved in lymphocyte trapping. A proprietary S1P1 receptor modulator library was screened for compounds with clear potency differences in β-arrestin recruitment and Gαi protein-mediated signaling...
December 4, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/29203226/innately-versatile-%C3%AE-%C3%AE-17%C3%A2-t-cells-in-inflammatory-and-autoimmune-diseases
#12
REVIEW
Pedro H Papotto, Annika Reinhardt, Immo Prinz, Bruno Silva-Santos
IL-17-producing γδ (γδ17) T cells form a versatile subset of cells that respond rapidly to innate stimuli and support the pro-inflammatory functions of different myeloid and lymphoid lineages, being particularly critical in the early stages of inflammatory and autoimmune responses. In mice, under homeostatic conditions, these innate-like lymphocytes are pre-programmed in the fetal thymus, through an intricate process involving both T cell receptor-dependent and -independent signals, which allows them to readily produce IL-17 upon stimulation...
December 1, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29187851/modulation-of-p2x7-receptor-during-inflammation-in-multiple-sclerosis
#13
Susanna Amadio, Chiara Parisi, Eleonora Piras, Paola Fabbrizio, Savina Apolloni, Cinzia Montilli, Sabina Luchetti, Serena Ruggieri, Claudio Gasperini, Franco Laghi-Pasini, Luca Battistini, Cinzia Volonté
Multiple sclerosis (MS) is characterized by macrophage accumulation and inflammatory infiltrates into the CNS contributing to demyelination. Because purinergic P2X7 receptor (P2X7R) is known to be abundantly expressed on cells of the hematopoietic lineage and of the nervous system, we further investigated its phenotypic expression in MS and experimental autoimmune encephalomyelitis conditions. By quantitative reverse transcription polymerase chain reaction and flow cytometry, we analyzed the P2X7R expression in human mononuclear cells of peripheral blood from stable and acute relapsing-remitting MS phases...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29158162/the-gelatinases-mmp-2-and-mmp-9-as-fine-tuners-of-neuroinflammatory-processes
#14
REVIEW
M-J Hannocks, X Zhang, H Gerwien, A Chashchina, M Burmeister, E Korpos, J Song, L Sorokin
This review focuses on the complementary roles of MMP-2 and MMP-9 in leukocyte migration into the brain in neuroinflammation, studied mainly in a murine model of experimental autoimmune encephalomyelitis (EAE) that has similarity to the human disease multiple sclerosis. We discuss the cellular sources of MMP-2/MMP-9 in EAE, their sites of activity, and how cleavage of the to-date identified MMP-2/MMP-9 substrates at the blood-brain barrier facilitate leukocyte filtration of the central nervous system (CNS)...
November 17, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29155234/survivin-and-autoimmunity-the-ins-and-outs
#15
REVIEW
Hamidreza Ebrahimiyan, Saeed Aslani, Nima Rezaei, Ahmadreza Jamshidi, Mahdi Mahmoudi
Autoimmunity is a status that immune mechanisms react against self-structure. The immune mechanisms, including cellular and molecular elements have been developed to immune body against foreign invades. Multiple factors such as genetic and epigenetic background, hormonal status, microbiome, and other factors can cause launching the autoreactive responses, in which the immune tolerance breaks and immune mechanisms are against self-antigens. Apoptosis is one of the important mechanisms in maintaining the tolerance and eliminating the autoreactive lymphocyte clones...
November 16, 2017: Immunology Letters
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
#16
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
#17
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
#18
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
#19
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
#20
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
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