title: Intracellular Protein Shuttling: A Mechanism Relevant for Myelin Repair in Multiple Sclerosis?
abstract: A prominent feature of demyelinating diseases such as multiple sclerosis (MS) is the degeneration and loss of previously established functional myelin sheaths, which results in impaired signal propagation and axonal damage. However, at least in early disease stages, partial replacement of lost oligodendrocytes and thus remyelination occur as a result of resident oligodendroglial precursor cell (OPC) activation. These cells represent a widespread cell population within the adult central nervous system (CNS) that can differentiate into functional myelinating glial cells to restore axonal functions. Nevertheless, the spontaneous remyelination capacity in the adult CNS is inefficient because OPCs often fail to generate new oligodendrocytes due to the lack of stimulatory cues and the presence of inhibitory factors. Recent studies have provided evidence that regulated intracellular protein shuttling is functionally involved in oligodendroglial differentiation and remyelination activities. In this review we shed light on the role of the subcellular localization of differentiation-associated factors within oligodendroglial cells and show that regulation of intracellular localization of regulatory factors represents a crucial process to modulate oligodendroglial maturation and myelin repair in the CNS.
authors.affiliation: Department of Neurology, Medical Faculty, University of Düsseldorf, 40225 Düsseldorf, Germany. Peter.Goettle@uni-duesseldorf.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Göttle
authors.affiliation: Department of Neurology, Medical Faculty, University of Düsseldorf, 40225 Düsseldorf, Germany. kuery@uni-duesseldorf.de.
authors.forename: Patrick
authors.initials: P
authors.lastname: Küry
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D009103:Multiple Sclerosis / Q000378:metabolism*; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism* / Q000502:physiology; D012038:Regeneration; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D009185:Myelin Proteins; D014157:Transcription Factors
keywords: differentiation inhibitors; multiple sclerosis; myelin repair; nucleocytoplasmic shuttling; oligodendrocyte; remyelination; transcription factors