The development of myelin repair agents for treatment of multiple sclerosis

Murphy, Robert P.; Murphy, Keith J.; Pickering, Mark

doi:10.4161/bioe.22835

Cited by 6 publications

(3 citation statements)

References 81 publications

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“…1 b). In addition, lysoPC is a known potent demyelinating agent either when injected into the spinal cord and other CNS regions or when applied to the PNS 43 – 45 . Since remyelination in the PNS is efficient and quick but limited by the presence of the demyelinating agent 46 , treatments to lower lysoPC might be considered in GBS therapeutics.…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid lipidomic biomarker signatures of demyelination for multiple sclerosis and Guillain–Barré syndrome

Péter

Török

Petrovics-Balog

et al. 2020

Sci Rep

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Multiple sclerosis (MS) and Guillain–Barré syndrome (GBS) are demyelinating disorders affecting the central nervous system and peripheral nervous system (PNS), respectively. Cerebrospinal fluid (CSF) is one of the most valuable sources of diagnostic biomarkers in neurological diseases. In the present study high sensitivity shotgun mass spectrometry was used to characterise the CSF lipidome of patients with MS, GBS and controls with non-demyelinating diseases. The quantification of 222 CSF lipid molecular species revealed characteristic changes in the absolute and relative lipid concentrations in MS and GBS compared to the controls. For the GBS group, the fourfold elevation in the total lipid content was a discriminatory and a newly identified feature of PNS demyelination. In contrast, in MS, the accumulation of the myelin-derived cerebrosides represented a specific feature of demyelination. As a common feature of demyelination, we identified upregulated levels of lipid metabolic intermediates. We found strong positive correlation between total protein content and lipid concentrations in both diseases. By exploring the CSF lipidome we demonstrate usefulness of broad-range shotgun lipidomic analysis as a fast and reliable method of biomarker discovery in patients with demyelinating neurological disorders that might be a valuable diagnostic complement to existing examinations.

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Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid lipidomic biomarker signatures of demyelination for multiple sclerosis and Guillain–Barré syndrome

Péter

Török

Petrovics-Balog

et al. 2020

Sci Rep

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“…A large number of studies showed that BMPs played an important role in the integrity of BBB [ 14 ]. S1P and S1PRs were involved in cell adhesion, migration, and BBB permeability changes [ 15 ]. In this study, it was found that the expression level of S1PR2 in pericytes of rats transfected with miR-149-5p showed a trend of increasing firstly and then decreasing after acute ischemia perfusion.…”

Section: Discussionmentioning

confidence: 99%

Analysis of regulatory effect of miR-149-5p on Sphingosine-1-phosphate receptor 2 of pericytes and its neuroprotective molecular mechanism after acute cerebral ischemia reperfusion in rats

et al. 2021

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To investigate the effect of miR-149-5p on sphingosine-1-phosphate receptor 2 (S1PR2) expression level and contents of matrix metalloproteinase (MMP-9) and superoxide dismutase (SOD) in the pericytes after acute cerebral ischemia reperfusion in rats, so as to clarify the neuroprotective molecular mechanism induced by miR-149-5p and provide references for the treatment of neurological diseases, 60 male SD rats aged 7-8 weeks were selected and divided randomly into test group (establishing middle cerebral artery occlusion (MCAO) model) and control group (no modeling). Rat pericytes and peripheral cerebral infarction tissues were collected 12 h, 1 d, 3 d, 5 d, and 7 d after MCAO modeling, respectively. The pericytes were identified by immunofluorescence assay (IFA) and transfected with miR-149-5p. Fluorescence quantitative PCR (FQPCR) and Western blot were adopted to detect S1PR2 expression level. The expression of S1PR2 in MCAO model rats was detected by IFA. Immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) were used to detect the changes of MMP9 protein and mRNA levels of SOD1, SOD2, and SOD3 in brain tissue. The results showed that mRNA level and protein expression level of S1PR2 in the test group were higher than those in the control group three days after MCAO modeling (P < 0.05); the expression of S1PR2 increased 12 h after MCAO modeling and returned to the normal level on the 5th day, and the content of MMP9 protein in brain tissue of the test group was significantly lower than that of the control group (P < 0.05); the mRNA levels and SODs activity of SOD1, SOD2, and SOD3 in the test group were higher than those in the control group (P < 0.05). Therefore, miR-149-5p played a neuroprotective role by regulating S1PR2 to change the expression levels of SODS and MMP9.

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“…The general failure of endogenous remyelination and inflammation-related axonal damage lead to accumulated neurological disability [ 2 ]. The current immunomodulating drugs for MS, such as interferon β , glatiramer acetate, and natalizumab, prevent inflammatory damage to the CNS, which do not effectively prevent the progressive clinical neurological decline most likely because they lack a direct action on CNS axons and myelin [ 3 ]. Neural stem cells (NSCs), which can differentiate into various neural cell types [ 2 , 4 ] and have myelinogenic potential [ 5 ] in the injured areas, have been introduced as a promising cell type of replacement therapy.…”

Section: Introductionmentioning

confidence: 99%

Transplantation of Neural Stem Cells Cotreated with Thyroid Hormone and GDNF Gene Induces Neuroprotection in Rats of Chronic Experimental Allergic Encephalomyelitis

Gao

Deng

et al. 2016

Neural Plasticity

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The present study investigates whether transplantation of NSCs treated with T3 alone (T3/NSCs), or in conjunction with GDNF gene (GDNF-T3/NSCs), provides a better therapeutic effect than NSCs for chronic EAE. EAE rats were, respectively, injected with NSCs, T3/NSCs, GDNF-T3/NSCs, and saline at 10 days and sacrificed at 60 days after EAE immunization. The three cell grafted groups showed a significant reduction in clinical scores, inflammatory infiltration, and demyelination compared with the saline-injected group, and among the cell grafted groups, the reduction in GDNF-T3/NSCs group was the most notable, followed by T3/NSCs group. Grafted T3/NSCs and GDNF-T3/NSCs acquired more MAP2, GalC, and less GFAP in brain compared with grafted NSCs, and grafted GDNF-T3/NSCs acquired most MAP2 and least GalC among the cell grafted groups. Furthermore, T3/NSCs and GDNF-T3/NSCs grafting increased the expression of mRNA for PDGFαR, GalC, and MBP in lesion areas of brain compared with NSCs grafting, and the expression of mRNA for GalC and MBP in GDNF-T3/NSCs group was higher than that in T3/NSCs group. In conclusion, T3/NSCs grafting, especially GDNF-T3/NSCs grafting, provides a better neuroprotective effect for EAE than NSCs transplantation.

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The development of myelin repair agents for treatment of multiple sclerosis

Cited by 6 publications

References 81 publications

Cerebrospinal fluid lipidomic biomarker signatures of demyelination for multiple sclerosis and Guillain–Barré syndrome

Cerebrospinal fluid lipidomic biomarker signatures of demyelination for multiple sclerosis and Guillain–Barré syndrome

Analysis of regulatory effect of miR-149-5p on Sphingosine-1-phosphate receptor 2 of pericytes and its neuroprotective molecular mechanism after acute cerebral ischemia reperfusion in rats

Transplantation of Neural Stem Cells Cotreated with Thyroid Hormone and GDNF Gene Induces Neuroprotection in Rats of Chronic Experimental Allergic Encephalomyelitis

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