Protective effects of matrine on experimental autoimmune encephalomyelitis via regulation of ProNGF and NGF signaling.
Exp Mol Pathol
; 100(2): 337-43, 2016 Apr.
Article
em En
| MEDLINE
| ID: mdl-26681653
ABSTRACT
Inflammation, demyelination, oligodendrocyte (OLG) death, and axonal degeneration are primary characteristics of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). OLGs generate myelin sheaths that surround axons, while damage to OLGs leads to demyelination and neurological functional deficit. Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae Flave, has been recently found to effectively ameliorate clinical signs in EAE. Its therapeutic mechanism has, however, not been completely elucidated. In the present study, we found that MAT retarded the disease process, attenuated the clinical severity of EAE rats, ameliorated inflammation and demyelination, and suppressed the apoptosis of OLGs in the central nervous system (CNS) of EAE rats. In addition, MAT markedly blocked increased expression of the proNGF-p75(NTR) death signaling complex, which is known to mediate OLG death in EAE animals. At the same time, MAT also prevented a decrease in the levels of NGF and its receptor TrkA, which together mediate the cell survival pathway and differentiation of OLGs. ProNGF, NGF, and the downstream effector proteins play an important role in the growth, differentiation, and apoptosis of OLGs as well as the reparative response to neuronal damage. These findings thus indicate that MAT improves clinical severity of EAE in part by reducing OLG apoptosis via restoring the ratios of proNGFNGF and the respective receptors p75(NTR)TrkA in vivo. Taken together, these results suggest that MAT may be a promising agent for MS treatment based on its protective effect on OLGs.
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Texto completo:
1
Base de dados:
MEDLINE
Métodos Terapêuticos e Terapias MTCI:
Terapias_biologicas
Assunto principal:
Precursores de Proteínas
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Quinolizinas
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Transdução de Sinais
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Alcaloides
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Encefalomielite Autoimune Experimental
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Fatores de Crescimento Neural
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Exp Mol Pathol
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
China