Remyelination in the CNS: From Biology to Therapy

Department of Veterinary Medicine and Cambridge Centre for Brain Repair, University of Cambridge, Madingley Road, Cambridge, CB3 0ES, UK.
Nature Reviews Neuroscience (Impact Factor: 31.43). 12/2008; 9(11):839-55. DOI: 10.1038/nrn2480
Source: PubMed


Remyelination involves reinvesting demyelinated axons with new myelin sheaths. In stark contrast to the situation that follows loss of neurons or axonal damage, remyelination in the CNS can be a highly effective regenerative process. It is mediated by a population of precursor cells called oligodendrocyte precursor cells (OPCs), which are widely distributed throughout the adult CNS. However, despite its efficiency in experimental models and in some clinical diseases, remyelination is often inadequate in demyelinating diseases such as multiple sclerosis (MS), the most common demyelinating disease and a cause of neurological disability in young adults. The failure of remyelination has profound consequences for the health of axons, the progressive and irreversible loss of which accounts for the progressive nature of these diseases. The mechanisms of remyelination therefore provide critical clues for regeneration biologists that help them to determine why remyelination fails in MS and in other demyelinating diseases and how it might be enhanced therapeutically.

63 Reads
  • Source
    • "This debris can create a dense matrix that may present a physical barrier to the demyelinated axon (although this has not been formally demonstrated). Previous studies have shown that myelin debris does not affect the number of OPCs recruited to the lesion site; however, differentiation of OPCs into myelinating oligodendrocytes is impaired by the extracellular accumulation of debris (Franklin and Kotter, 2008; Kuhlmann et al., 2008). Cultured OPCs plated onto CNS myelin substrates "

    Neuroinflammation: New Insights into Beneficial and Detrimental Functions, 1 edited by Sam David, 01/2015: chapter Effects of Macrophages and Monocytes in Remyelination of the CNS: pages 15; John Wiley & Sons., ISBN: 1118732804
  • Source
    • "The loss of oligodendrocytes may be replaced by proliferating nerve/glial antigen 2 (NG2) cells, also known as oligodendrocyte precursor cells (Tripathi and McTigue, 2007). These OPCs are able to migrate to the damaged site and differentiate into mature myelinating oligodendrocytes if the environment is permissive (Franklin and Ffrench-Constant, 2008). For instance, degenerated myelin contains inhibitory molecules such as NogoA, Oligodendrocyte-myelin glycoprotein (OMgp) and myelin-associated glycoprotein (MAG). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Besides myelination of neuronal axons by oligodendrocytes to facilitate propagation of action potentials, oligodendrocytes also support axon survival and function. A key transcription factor involved in these processes is nuclear factor-κB (NF-κB), a hetero or homodimer of the Rel family of proteins, including p65, c-Rel, RelB, p50, and p52. Under unstimulated, NF-κB remains inactive in the cytoplasm through interaction with NF-κB inhibitors (IκBs). Upon activation of NF-κB the cytoplasmic IκBs gets degradated, allowing the translocation of NF-κB into the nucleus where the dimer binds to the κB consensus DNA sequence and regulates gene transcription. In this review we describe how oligodendrocytes are, directly or indirectly via neighboring cells, regulated by NF-κB signaling with consequences for innate and adaptive immunity and for regulation of cell apoptosis and survival.
    Frontiers in Molecular Neuroscience 05/2014; 7:47. DOI:10.3389/fnmol.2014.00047 · 4.08 Impact Factor
  • Source
    • "Since both Olig2 and Nogo-A are expressed in the oligodendrocyte lineage cells, it suggests a possibility that inhibition of NgR1 activation could induce differentiation of NSPs into oligodendrocytes, but the cells could not survive in the in vitro conditions. Since oligodendrocytes can promote survival of neuronal cells3334, the transient increase in oligodendrocyte population could contribute to the augmented proportion of neuronal cells observed in the differentiation Day 10. Our results indicated that inhibition of NgR1 in adult NSCs can promote neuronal cell production. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Inhibition of Nogo-66 receptor (NgR) can promote recovery following spinal cord injury. The ecto-domain of NgR can be phosphorylated by protein kinase A (PKA), which blocks activation of the receptor. Here, we found that infusion of PKA plus ATP into the damaged spinal cord can promote recovery of locomotor function. While significant elongation of cortical-spinal axons was not detectable even in the rats showing enhanced recovery, neuronal precursor cells were observed in the region where PKA plus ATP were directly applied. NgR1 was expressed in neural stem/progenitor cells (NSPs) derived from the adult spinal cord. Both an NgR1 antagonist NEP1-40 and ecto-domain phosphorylation of NgR1 promote neuronal cell production of the NSPs, in vitro. Thus, inhibition of NgR1 in NSPs can promote neuronal cell production, which could contribute to the enhanced recovery of locomotor function following infusion of PKA and ATP.
    Scientific Reports 05/2014; 4:4972. DOI:10.1038/srep04972 · 5.58 Impact Factor
Show more