Axonal degeneration in multiple sclerosis: defining therapeutic targets by identifying the causes of pathology

2015 ◽  
Vol 5 (6) ◽  
pp. 527-548 ◽  
Author(s):  
Jae Young Lee ◽  
Melissa Biemond ◽  
Steven Petratos
Keyword(s):  
Multiple Sclerosis ◽  
Axonal Degeneration ◽  
Therapeutic Targets

scholarly journals Novel Therapeutic Targets for Axonal Degeneration in Multiple Sclerosis

2010 ◽  
Vol 69 (4) ◽  
pp. 323-334 ◽  
Author(s):  
Steven Petratos ◽  
Michael F. Azari ◽  
Ezgi Ozturk ◽  
Roula Papadopoulos ◽  
Claude C.A. Bernard
Keyword(s):  
Multiple Sclerosis ◽  
Axonal Degeneration ◽  
Therapeutic Targets ◽  
Novel Therapeutic

Remyelination of Demyelinated CNS Axons by Transplanted Human Schwann Cells: The Deleterious Effect of Contaminating Fibroblasts

2001 ◽  
Vol 10 (3) ◽  
pp. 305-315 ◽  
Author(s):  
C. M. H. Brierley ◽  
A. J. Crang ◽  
Y. Iwashita ◽  
J. M. Gilson ◽  
N. J. Scolding ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Axonal Degeneration ◽  
Autologous Transplantation ◽  
Growth Factor Receptor ◽  
Adult Rats ◽  
Demyelinating Lesions ◽  
Cell Implantation

Areas of demyelination can be remyelinated by transplanting myelin-forming cells. Schwann cells are the naturally remyelinating cells of the peripheral nervous system and have a number of features that may make them attractive for cell implantation therapies in multiple sclerosis, in which spontaneous but limited Schwann cell remyelination has been well documented. Schwann cells can be expanded in vitro, potentially affording the opportunity of autologous transplantation; and they might also be spared the demyelinating process in multiple sclerosis. Although rat, cat, and monkey Schwann cells have been transplanted into rodent demyelinating lesions, the behavior of transplanted human Schwann cells has not been evaluated. In this study we examined the consequences of injecting human Schwann cells into areas of acute demyelination in the spinal cords of adult rats. We found that transplants containing significant fibroblast contamination resulted in deposition of large amounts of collagen and extensive axonal degeneration. However, Schwann cell preparations that had been purified by positive immunoselection using antibodies to human low-affinity nerve growth factor receptor containing less than 10% fibroblasts were associated with remyelination. This result indicates that fibroblast contamination of human Schwann cells represents a greater problem than would have been appreciated from previous studies.

scholarly journals The meninges: new therapeutic targets for multiple sclerosis

2015 ◽  
Vol 165 (2) ◽  
pp. 255-269 ◽  
Author(s):  
Abigail E. Russi ◽  
Melissa A. Brown
Keyword(s):  
Multiple Sclerosis ◽  
Therapeutic Targets ◽  
New Therapeutic Targets

Biological markers in CSF and blood for axonal degeneration in multiple sclerosis

2005 ◽  
Vol 4 (1) ◽  
pp. 32-41 ◽  
Author(s):  
Charlotte E Teunissen ◽  
Christine Dijkstra ◽  
Chris Polman
Keyword(s):  
Multiple Sclerosis ◽  
Biological Markers ◽  
Axonal Degeneration

scholarly journals Nav1.6 promotes inflammation and neuronal degeneration in a mouse model of multiple sclerosis

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Barakat Alrashdi ◽  
Bassel Dawod ◽  
Andrea Schampel ◽  
Sabine Tacke ◽  
Stefanie Kuerten ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Retinal Ganglion Cells ◽  
Axonal Degeneration ◽  
Ganglion Cells ◽  
Neuronal Degeneration ◽  
Retinal Ganglion ◽  
Autoimmune Encephalomyelitis ◽  
Aav Vector ◽  
Α Subunit

Abstract Background In multiple sclerosis (MS) and in the experimental autoimmune encephalomyelitis (EAE) model of MS, the Nav1.6 voltage-gated sodium (Nav) channel isoform has been implicated as a primary contributor to axonal degeneration. Following demyelination Nav1.6, which is normally co-localized with the Na+/Ca2+ exchanger (NCX) at the nodes of Ranvier, associates with β-APP, a marker of neural injury. The persistent influx of sodium through Nav1.6 is believed to reverse the function of NCX, resulting in an increased influx of damaging Ca2+ ions. However, direct evidence for the role of Nav1.6 in axonal degeneration is lacking. Methods In mice floxed for Scn8a, the gene that encodes the α subunit of Nav1.6, subjected to EAE we examined the effect of eliminating Nav1.6 from retinal ganglion cells (RGC) in one eye using an AAV vector harboring Cre and GFP, while using the contralateral either injected with AAV vector harboring GFP alone or non-targeted eye as control. Results In retinas, the expression of Rbpms, a marker for retinal ganglion cells, was found to be inversely correlated to the expression of Scn8a. Furthermore, the gene expression of the pro-inflammatory cytokines Il6 (IL-6) and Ifng (IFN-γ), and of the reactive gliosis marker Gfap (GFAP) were found to be reduced in targeted retinas. Optic nerves from targeted eyes were shown to have reduced macrophage infiltration and improved axonal health. Conclusion Taken together, our results are consistent with Nav1.6 promoting inflammation and contributing to axonal degeneration following demyelination.

scholarly journals Role of inflammasomes in multiple sclerosis and their potential as therapeutic targets

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Vaidya Govindarajan ◽  
Juan Pablo de Rivero Vaccari ◽  
Robert W. Keane
Keyword(s):  
Multiple Sclerosis ◽  
Therapeutic Targets
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