期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 746, 期 -, 页码 301-307出版社
ELSEVIER
DOI: 10.1016/j.ejphar.2014.09.023
关键词
Endoplasmic reticulum stress; Parkinson's disease; Zonisamide
资金
- Sumitomo Dainippon Pharma Co., Ltd (Osaka, Japan)
Zonisamide has been reported to have protective effects on epilepsy and Parkinson's disease and to work via various mechanisms of action, such as inhibition of monoamine oxidase-B and enhancement of tyrosine hydroxylase. Recently, it has been suggested that zonisamide itself shows neuroprotective actions. Therefore, in the present study we investigated the neuroprotective effects of zonisamide against endoplasmic reticulum (ER) stress. We used human neuroblastoma (SH-SY5Y) cells and investigated the protective effects of zonisamide against tunicamycin- and thapsigargin-induced neuronal cell death. In addition, we investigated the effect of zonisamide against 1-methyl-4-phenylpyridinium (MPP+)-induced cell death and the mechanism of protection against ER stress. In vivo, we investigated the effect of zonisamide (20 mg/kg, p.o.) in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-inducecl mouse model of Parkinson's disease. Zonisamide not only suppressed MPP+-induced cell death, but also inhibited ER stress-induced cell death and suppressed the expression of ER stress-related factors such as C/EBO homologous protein (CHOP) in vivo. Furthermore, zonisamide inhibited the activation of caspase-3 in vitro. These results suggest that zonisamide affected ER stress via caspase-3. We think that ER stress, particularly the mechanism via caspase-3, is involved in part of the neuroprotective effect of zonisamide against the experimental models of Parkinson's disease. (C) 2014 Elsevier B.V. All rights reserved.
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