Do central nervous system axons remyelinate?
In multiple sclerosis (MS), one of the most frequent demyelinating diseases in man, remyelination of demyelinating lesions exists but is often incomplete. Also reported in experimental models of demyelination, this phenomenom confirms the regenerating potential of the demyelinated central nervous system (CNS) and, in particular, the existence of an endogenous mechanism of oligodendrocyte renewal. Failure in efficient remyelination could result from exhaustion of the pool of remyelinating cells, loss of axons and absence of a permissive environment for remyelination. Identifying the nature and the origin of the cells capable of generating new oligodendrocytes for remyelination could contribute to strategies to activate these cells, and thereby enhance their potential for myelin repair. Within the adult CNS, several cell types are capable of generating new oligodendrocytes following myelin damage: post-mitotic oligodendrocytes frequently found at the lesion site, oligodendrocyte progenitors whose existence has been confirmed both in vitro and in vivo, and multipotent cells localized in the germinative areas of the brain and the spinal cord. Although restricted to particular sites of the CNS, these multipotent cells, which maintain the capacity to self-renew and to migrate throughout adulthood, could constitute a powerful source of remyelinating cells. The study of the mechanisms of proliferation, migration and differentiation of these cells in response to demyelination should allow the definition of new strategies to promote endogenous remyelination and develop therapeutic approaches for demyelinating diseases such as MS. This goal is an appealing alternative to the transplantation of myelin-forming cells and should efficiently complement strategies aimed at reducing neuronal loss and inflammation.
Nait-Oumesmar
B
B
Brookdale Center for Molecular Biology, Mount Sinai School of Medicine, New York 10029-6574, USA.
Lachapelle
F
F
Decker
L
L
Baron-Van Evercooren
A
A
D000818:Animals; D001369:Axons / Q000502:physiology*; D002490:Central Nervous System / Q000648:ultrastructure*; D006801:Humans; D009103:Multiple Sclerosis; D009186:Myelin Sheath / Q000502:physiology*; D009836:Oligodendroglia / Q000502:physiology; D013234:Stem Cells / Q000502:physiology