Merck
  • Home
  • Search Results
  • Non-steroidal anti-inflammatory drug indometacin enhances endogenous remyelination.

Non-steroidal anti-inflammatory drug indometacin enhances endogenous remyelination.

Acta neuropathologica (2015-05-07)
Anna Preisner, Stefanie Albrecht, Qiao-Ling Cui, Stephanie Hucke, Julia Ghelman, Christine Hartmann, Makoto Mark Taketo, Jack Antel, Luisa Klotz, Tanja Kuhlmann
ABSTRACT

Multiple sclerosis is the most frequent demyelinating disease in the CNS that is characterized by inflammatory demyelinating lesions and axonal loss, the morphological correlate of permanent clinical disability. Remyelination does occur, but is limited especially in chronic disease stages. Despite effective immunomodulatory therapies that reduce the number of relapses the progressive disease phase cannot be prevented. Therefore, promotion of neuroprotective and repair mechanisms, such as remyelination, represents an attractive additional treatment strategy. A number of pathways have been identified that may contribute to impaired remyelination in MS lesions, among them the Wnt/β-catenin pathway. Here, we demonstrate that indometacin, a non-steroidal anti-inflammatory drug (NSAID) that has been also shown to modulate the Wnt/β-catenin pathway in colorectal cancer cells promotes differentiation of primary human and murine oligodendrocytes, myelination of cerebellar slice cultures and remyelination in cuprizone-induced demyelination. Our in vitro experiments using GSK3β inhibitors, luciferase reporter assays and oligodendrocytes expressing a mutant, dominant stable β-catenin indicate that the mechanism of action of indometacin depends on GSK3β activity and β-catenin phosphorylation. Indometacin might represent a promising treatment option to enhance endogenous remyelination in MS patients.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
MISSION® esiRNA, targeting human PDGFRA
Sigma-Aldrich
Ethylenediaminetetraacetic acid, 99.995% trace metals basis
Sigma-Aldrich
Triton X-100, laboratory grade
Sigma-Aldrich
Ethylenediaminetetraacetic acid, anhydrous, crystalline, BioReagent, suitable for cell culture
Sigma-Aldrich
Aspirin, meets USP testing specifications
Sigma-Aldrich
Ethylenediaminetetraacetic acid, purified grade, ≥98.5%, powder
Sigma-Aldrich
Ethylenediaminetetraacetic acid, ACS reagent, 99.4-100.6%, powder
Sigma-Aldrich
Ethylenediaminetetraacetic acid, BioUltra, anhydrous, ≥99% (titration)
Sigma-Aldrich
Ethylenediaminetetraacetic acid solution, 0.02% in DPBS (0.5 mM), sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
Lithium chloride, AnhydroBeads, −10 mesh, ≥99.9% trace metals basis
Sigma-Aldrich
Lithium chloride solution, 8 M, for molecular biology, ≥99%
Sigma-Aldrich
Lithium chloride, powder, ≥99.98% trace metals basis
Sigma-Aldrich
Ethylene glycol-bis(2-aminoethylether)-N,N,N′,N′-tetraacetic acid, BioXtra, ≥97 .0%
Sigma-Aldrich
Lithium chloride, BioXtra, ≥99.0% (titration)
Sigma-Aldrich
Phenylmethanesulfonyl fluoride, ≥98.5% (GC)
Sigma-Aldrich
PIPES, BioXtra, for molecular biology, ≥99.5% (T)
Sigma-Aldrich
Lithium chloride, BioUltra, for molecular biology, anhydrous, ≥99.0% (AT)
Sigma-Aldrich
Phenylmethanesulfonyl fluoride, ≥99.0% (T)
Sigma-Aldrich
Lithium-7Li chloride, 99 atom % 7Li, 99% (CP)
Sigma-Aldrich
DL-Dithiothreitol solution, BioUltra, for molecular biology, ~1 M in H2O
Sigma-Aldrich
Phosphatase Inhibitor Cocktail 2, aqueous solution (dark coloration may develop upon storage, which does not affect the activity)
Sigma-Aldrich
Lithium chloride, AnhydroBeads, −10 mesh, 99.998% trace metals basis
Sigma-Aldrich
PIPES, BioXtra, ≥99% (titration)
Sigma-Aldrich
PIPES, ≥99% (titration)
Sigma-Aldrich
PIPES, BioPerformance Certified, suitable for cell culture
Sigma-Aldrich
Acetylsalicylic acid, analytical standard
Sigma-Aldrich
Ethylene glycol-bis(2-aminoethylether)-N,N,N′,N′-tetraacetic acid, for molecular biology, ≥97.0%
Sigma-Aldrich
Acetylsalicylic acid, ≥99.0%
Sigma-Aldrich
Ethylene glycol-bis(2-aminoethylether)-N,N,N′,N′-tetraacetic acid, ≥97.0%
Sigma-Aldrich
Lithium chloride, for molecular biology, ≥99%