Hyaluronan accumulates in demyelinated lesions and inhibits oligodendrocyte progenitor maturation.
Nat Med
; 11(9): 966-72, 2005 Sep.
Article
em En
| MEDLINE
| ID: mdl-16086023
ABSTRACT
Demyelination is the hallmark of numerous neurodegenerative conditions, including multiple sclerosis. Oligodendrocyte progenitors (OPCs), which normally mature into myelin-forming oligodendrocytes, are typically present around demyelinated lesions but do not remyelinate affected axons. Here, we find that the glycosaminoglycan hyaluronan accumulates in demyelinated lesions from individuals with multiple sclerosis and in mice with experimental autoimmune encephalomyelitis. A high molecular weight (HMW) form of hyaluronan synthesized by astrocytes accumulates in chronic demyelinated lesions. This form of hyaluronan inhibits remyelination after lysolecithin-induced white matter demyelination. OPCs accrue and do not mature into myelin-forming cells in demyelinating lesions where HMW hyaluronan is present. Furthermore, the addition of HMW hyaluronan to OPC cultures reversibly inhibits progenitor-cell maturation, whereas degrading hyaluronan in astrocyte-OPC cocultures promotes oligodendrocyte maturation. HMW hyaluronan may therefore contribute substantially to remyelination failure by preventing the maturation of OPCs that are recruited to demyelinating lesions.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligodendroglia
/
Astrócitos
/
Doenças Desmielinizantes
/
Receptores de Hialuronatos
/
Ácido Hialurônico
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
MEDICINA
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Estados Unidos