Expansion of oligodendrocyte progenitor cells following SIRT1 inactivation in the adult brain.
Nat Cell Biol
; 15(6): 614-24, 2013 Jun.
Article
em En
| MEDLINE
| ID: mdl-23644469
ABSTRACT
Oligodendrocytes-the myelin-forming cells of the central nervous system-can be regenerated during adulthood. In adults, new oligodendrocytes originate from oligodendrocyte progenitor cells (OPCs), but also from neural stem cells (NSCs). Although several factors supporting oligodendrocyte production have been characterized, the mechanisms underlying the generation of adult oligodendrocytes are largely unknown. Here we show that genetic inactivation of SIRT1, a protein deacetylase implicated in energy metabolism, increases the production of new OPCs in the adult mouse brain, in part by acting in NSCs. New OPCs produced following SIRT1 inactivation differentiate normally, generating fully myelinating oligodendrocytes. Remarkably, SIRT1 inactivation ameliorates remyelination and delays paralysis in mouse models of demyelinating injuries. SIRT1 inactivation leads to the upregulation of genes involved in cell metabolism and growth factor signalling, in particular PDGF receptor α (PDGFRα). Oligodendrocyte expansion following SIRT1 inactivation is mediated at least in part by AKT and p38 MAPK-signalling molecules downstream of PDGFRα. The identification of drug-targetable enzymes that regulate oligodendrocyte regeneration in adults could facilitate the development of therapies for demyelinating injuries and diseases, such as multiple sclerosis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oligodendroglia
/
Receptor alfa de Fator de Crescimento Derivado de Plaquetas
/
Sirtuína 1
/
Células-Tronco Neurais
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article