Search results for "multiple sclerosis"
showing 10 items of 630 documents
Myelin Basic Protein synthesis is regulated by small non‐coding RNA 715
2012
Oligodendroglial Myelin Basic Protein (MBP) synthesis is essential for myelin formation in the central nervous system. During oligodendrocyte differentiation, MBP mRNA is kept in a translationally silenced state while intracellularly transported, until neuron-derived signals initiate localized MBP translation. Here we identify the small non-coding RNA 715 (sncRNA715) as an inhibitor of MBP translation. SncRNA715 localizes to cytoplasmic granular structures and associates with MBP mRNA transport granule components. We also detect increased levels of sncRNA715 in demyelinated chronic human multiple sclerosis lesions, which contain MBP mRNA but lack MBP protein.
Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
2013
International audience; Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variant…
IL12A, MPHOSPH9/CDK2AP1 and RGS1 are novel multiple sclerosis susceptibility loci
2010
A recent meta-analysis identified seven single-nucleotide polymorphisms (SNPs) with suggestive evidence of association with multiple sclerosis (MS). We report an analysis of these polymorphisms in a replication study that includes 8,085 cases and 7,777 controls. A meta-analysis across the replication collections and a joint analysis with the discovery data set were performed. The possible functional consequences of the validated susceptibility loci were explored using RNA expression data. For all of the tested SNPs, the effect observed in the replication phase involved the same allele and the same direction of effect observed in the discovery phase. Three loci exceeded genome-wide significa…
Remyelinating strategies in multiple sclerosis.
2014
Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disorder of the CNS characterized by infiltration of immune cells and progressive damage to myelin sheaths and neurons. In recent years, the importance of the neuronal compartment in the early pathology of multiple sclerosis has become increasingly clear. Direct axonal damage within the early stages of inflammation as well as neuronal injury as a result of chronic demyelination are essential factors for the development of long-term disability in patients. Viewing MS as both inflammatory and neurodegenerative has significant implications for treatment, with remyelination of denuded axons to protect neurons from dam…
Neuronal injury in chronic CNS inflammation.
2010
Introduction Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system which is characterized by inflammatory demyelination and neurodegeneration. Neurological symptoms include sensory disturbances, optic neuritis, limb weakness, ataxia, bladder dysfunction, cognitive deficits and fatigue. Pathophysiology The inflammation process with MS is promoted by several inflammatory cytokines produced by the immune cells themselves and local resident cells like activated microglia. Consecutive damaging pathways involve the transmigration of activated B lymphocytes and plasma cells, which synthesize antibodies against the myelin sheath, boost the immune atta…
Neurodegeneration in multiple sclerosis: novel treatment strategies.
2012
In recent years it has become clear that the neuronal compartment already plays an important role early in the pathology of multiple sclerosis (MS). Neuronal injury in the course of chronic neuroinflammation is a key factor in determining long-term disability in patients. Viewing MS as both inflammatory and neurodegenerative has major implications for therapy, with CNS protection and repair needed in addition to controlling inflammation. Here, the authors' review recently elucidated molecular insights into inflammatory neuronal/axonal pathology in MS and discuss the resulting options regarding neuroprotective and regenerative treatment strategies.
Multiple sclerosis patients show an increased spontaneous activity of their peripheral blood monocytes as measured by chemiluminescence
1983
I has been reported that myelin basic protein (BP) reacts extremely sensitively to peroxide, which is formed when monocytes/macrophages are stimulated to produce a "respiratory burst" (RB). We measured the RB activity by means of chemiluminescence in peripheral blood monocytes/macrophages (MO) of 17 MS patients, 5 patients with a viral infection of the CNS, and 14 control persons. The median of the spontaneous RB activity of MS patients compared with the median of our control group showed a highly significant increase (P = 0.0002). All MS patients examined possessed a clearly increased MO activity. The highest values, however, were found in MS patients in a bout (means = 315%, means = 296%)…
Ferrocenyl glycopeptides as electrochemical probes to detect autoantibodies in multiple sclerosis patients' será
2008
Abstract Glycopeptide analogues of CSF114(Glc), modified at N-terminus with new ferrocenyl carboxylic acid and a new ferrocenyl-thiphosphino amino acid, were used to implement a new electrochemical biosensor for autoantibody detection in multiple sclerosis. The ferrocenyl moiety of these "electrochemical probes" did not affect autoantibody recognition both in SP-ELISA and in inhibition experiments. By electrochemical monitoring the interactions of the modified peptides Fc-CSF114(Glc) and 4-FcPhP(S)Abu-CSF114(Glc) with the autoantibodies, we demonstrated that autoantibodies could be detected with a sensitivity comparable to ELISA method. The new electrochemical probes can be proposed to char…
Towards a validated definition of the clinical transition to secondary progressive multiple sclerosis: A study from the Italian MS Register.
2022
Background: Definitions for reliable identification of transition from relapsing-remitting multiple sclerosis (MS) to secondary progressive (SP)MS in clinical cohorts are not available. Objectives: To compare diagnostic performances of two different data-driven SPMS definitions. Methods: Data-driven SPMS definitions based on a version of Lorscheider’s algorithm (DDA) and on the EXPAND trial inclusion criteria were compared, using the neurologist’s definition (ND) as gold standard, in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), Akaike information criterion (AIC) and area under the curve (AUC). Results: A cohort of 10,240 MS patients wi…
The Effect of Smoking on Long-term Gray Matter Atrophy and Clinical Disability in Patients with Relapsing-Remitting Multiple Sclerosis
2022
Background and ObjectivesThe relationship between smoking, long-term brain atrophy, and clinical disability in patients with multiple sclerosis (MS) is unclear. Here, we assessed long-term effects of smoking by evaluating MRI and clinical outcome measures after 10 years in smoking and nonsmoking patients with relapsing-remitting MS (RRMS).MethodsWe included 85 treatment-naive patients with RRMS with recent inflammatory disease activity who participated in a 10-year follow-up visit after a multicenter clinical trial of 24 months. Smoking status was decided for each patient by 2 separate definitions: by serum cotinine levels measured regularly for the first 2 years of the follow-up (during th…