Neuroprotective effects of phenylbutyrate against MPTP neurotoxicity
Neuroprotective effects of phenylbutyrate against MPTP neurotoxicity
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DOI：
10.1385/nmm:5:3:235
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发表时间：
2004-01-01
影响因子：
3.5
通讯作者：
Beal, MF
中科院分区：
文献类型：
--
作者：
Gardian, G;Yang, LC;Beal, MF
越来越多的证据表明，组蛋白去乙酰化酶（HDAC）抑制剂的管理可以通过多种机制发挥神经保护作用。苯丁酸酯是一种众所周知的HDAC抑制剂，其增加许多基因的基因转录，并且还发挥神经保护作用。这些包括几种抗氧化酶、分子伴侣和参与细胞存活的基因。我们研究了苯丁酸盐的给药是否可以对1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）产生显著的神经保护作用，MPTP已用于帕金森病模型。苯丁酸盐的管理显着衰减MPTP诱导的纹状体多巴胺和酪氨酸羟化酶阳性神经元在黑质的损失损耗。这些发现进一步证明，苯丁酸盐的给药可能是治疗神经退行性疾病的一种有用方法。
There is increasing evidence that administration of histone deacetylase (HDAC) inhibitors can exert neuroprotective effects by a variety of mechanisms. Phenylbutyrate is a well-known HDAC inhibitor, which increases gene transcription of a number of genes, and also exerts neuroprotective effects. These include several antioxiclant enzymes, chaperones, and genes involved in cell survival. We examined whether administration of phenylbutyrate could exert significant neuroprotective effects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which has been used to model Parkinson's disease. Administration of phenylbutyrate significantly attenuated MPTP-induced depletion of striatal dopamine and loss of tyrosine hydroxylase-positive neurons in the substantia nigra. These findings provide further evidence that administration of phenylbutyrate may be a useful approach for the treatment of neurodegenerative diseases.