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J Pharmacol Sci ; 133(3): 187-189, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28363412

RESUMO

FTY720 is an immunosuppressive multiple sclerosis (MS) drug that stimulates the expression of neuroprotective brain-derived-neurotrophic-factor (BDNF). In vivo preclinical data suggest that FTY720 could be beneficial for treating Parkinson's patients, though its immunosuppressive effects might limit its efficacy. Two novel FTY720-derivatives, FTY720-C2 and FTY720-Mitoxy, also stimulate BDNF expression and enter brain like FTY720 but are not phosphorylated, suggesting they will not produce FTY720-like immunosuppression. Using FTY720 as a positive control, we measured low and high dose FTY720-derivatives, which did not stimulate FTY720-like lymphopenia or immunosuppressive signaling. These findings support the further preclinical assessment of the derivatives as potential novel Parkinson's therapies.


Assuntos
Linfócitos/efeitos dos fármacos , Esfingosina/farmacologia , Animais , Linhagem Celular Tumoral , Feminino , Contagem de Leucócitos , Linfopenia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Neutrófilos/efeitos dos fármacos , Fosforilação , Receptores de Lisoesfingolipídeo/metabolismo , Esfingosina/análogos & derivados , Receptores de Esfingosina-1-Fosfato
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