Remyelinating strategies in multiple sclerosis

Abstract

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 damage being necessary in addition to controlling inflammation. Here, we review recent molecular insights into key molecules and pathways controlling the differentiation of oligodendrocyte progenitor cells and the regenerative process of remyelination in MS and discuss the resulting options regarding remyelinating treatment strategies.

Positron-emission tomography molecular imaging of glia and myelin in drug discovery for multiple sclerosis

“…Additional direct and quantitative myelin imaging methods are needed to support the development of new drugs to enhance remyelination [74].…”

Co-ultramicronized Palmitoylethanolamide/Luteolin Promotes the Maturation of Oligodendrocyte Precursor Cells

“…Intended to target the recurring inflammation of the disease, they do not necessarily ensure remyelination. Indeed, considerable efforts are now being directed to the next phase of MS therapy, namely, remyelination/regeneration 14 15 16 17 . The antimuscarinic antiparkinsonian agent benztropine has been reported to stimulate OPC differentiation in vitro and promote remyelination in mouse models of MS 14 .…”

Methylthioadenosine promotes remyelination by inducing oligodendrocyte differentiation

“…The myelin-axon unit is critical to maintain the trophism of long axons, and for the exchange of metabolites and macromolecules like lactate, Nacetyl Aspartate or lipids [4]. This metabolic relationship further reinforces the attractiveness of remyelination as a therapeutic strategy to preventing axon loss in the later stages of the disease [5]. Yet even if remyelination would have been efficient in the early stages of MS its effects might be limited in the long term, particularly given the resistance of adult oligodendrocyte precursor cells (OPCs) to differentiate into myelinating oligodendrocytes (OLs) [6] and the molecular changes in demyelinated axons that lead to the rejection of myelin (e.g.…”