TY - JOUR
T1 - Lessons from oligodendrocyte biology on promoting repair in multiple sclerosis
AU - Câmara, Joana
AU - Ffrench-Constant, Charles
PY - 2007/2
Y1 - 2007/2
N2 - The failure of remyelination in multiple sclerosis (MS) contributes to inadequate recovery of neurological function after episodes of active inflammation and demyelination. It is likely that identification of novel strategies to promote remyelination will stem from a better understanding of oligodendrocyte biology. Here we illustrate this point by highlighting four areas where recent advances have important implications for remyelination strategies. First, oligodendrocyte precursor cells arise from different regions during development, and the cells from these distinct sites may have important functional differences. It is, therefore, essential to determine which oligodendrocyte population contributes to remyelination in the adult. Second, the extracellular matrix and its integrin receptors contribute to the regulation of oligodendrocyte behaviour, providing a hitherto unexplored set of drug targets. Third, the mechanisms that regulate myelin sheath formation are distinct from those that promote the earlier stages of differentiation, requiring experimental strategies that model sheath formation rather than simply examining oligodendrocyte differentiation in the absence of axons. Lastly, inflammation can promote remyelination and repair as well as damaging the CNS, and identification of the pro-myelinogenic factors in the immune response may also point to new therapies for MS.
AB - The failure of remyelination in multiple sclerosis (MS) contributes to inadequate recovery of neurological function after episodes of active inflammation and demyelination. It is likely that identification of novel strategies to promote remyelination will stem from a better understanding of oligodendrocyte biology. Here we illustrate this point by highlighting four areas where recent advances have important implications for remyelination strategies. First, oligodendrocyte precursor cells arise from different regions during development, and the cells from these distinct sites may have important functional differences. It is, therefore, essential to determine which oligodendrocyte population contributes to remyelination in the adult. Second, the extracellular matrix and its integrin receptors contribute to the regulation of oligodendrocyte behaviour, providing a hitherto unexplored set of drug targets. Third, the mechanisms that regulate myelin sheath formation are distinct from those that promote the earlier stages of differentiation, requiring experimental strategies that model sheath formation rather than simply examining oligodendrocyte differentiation in the absence of axons. Lastly, inflammation can promote remyelination and repair as well as damaging the CNS, and identification of the pro-myelinogenic factors in the immune response may also point to new therapies for MS.
KW - Extracellular matrix
KW - Inflammation
KW - Integrin
KW - Laminin
KW - Neuregulin
KW - Oligodendrocyte precursor
KW - Remyelination
UR - http://www.scopus.com/inward/record.url?scp=33847309880&partnerID=8YFLogxK
U2 - 10.1007/s00415-007-1004-y
DO - 10.1007/s00415-007-1004-y
M3 - Review article
AN - SCOPUS:33847309880
VL - 254
SP - I/15-I/22
JO - Journal of Neurology
JF - Journal of Neurology
SN - 0340-5354
IS - 1 SUPPL.
ER -