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
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.
- "However, to date there are no substances available that can enhance remyelination. Remyelination is the result of recruitment/proliferation of new oligodendrocyte precursor cells (OPC) and differentiation into mature myelin producing oligodendrocytes (Franklin and Ffrench-Constant, 2008). These processes are supported by many factors and signals and failure at any stage might lead to repair failure. "
- "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 "
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- "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). "
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.
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