Apoptotic molecules and MPTP-induced cell death
Apoptotic molecules and MPTP-induced cell death
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DOI：
10.1016/s0892-0362(02)00213-1
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发表时间：
2002-09-01
影响因子：
2.9
通讯作者：
Parvez, SH
中科院分区：
文献类型：
--
作者：
Nicotra, A;Parvez, SH
MPTP诱导的神经毒性是研究帕金森病（PD）发病机制最常用的实验模型之一。在体内给予小鼠的MPTP导致黑质（SN）中多巴胺能神经元的选择性损失，如在这种疾病中。当使用神经元细胞培养物时，MPTP的活性代谢产物MPP+可在体外诱导细胞死亡。MPTP/MPP+诱导细胞死亡的生化机制仍有待完全阐明。本文综述了最近的一些研究结果连接MPTP/MPP+的影响与分子通常参与细胞凋亡途径。这种类型的研究已经广泛使用了基因操作系统，如转基因小鼠和转染细胞系。已有证据表明，Bcl-2、Bax、JNK和半胱天冬酶与小鼠体内MPTP给药引起的神经毒性作用有关。不同的神经元细胞系，如MN 9D细胞，SH-SY 5 Y细胞，小脑颗粒神经元，皮质神经元，和GH 3细胞也进行了测试，以研究Bcl-2，Bax，和半胱天冬酶在体外MPP+诱导的神经毒性的可能参与。(C)2002年爱思唯尔科技有限公司All rights reserved.
MPTP-induced neurotoxicity is one of the experimental models most commonly used to study the pathogenesis of Parkinson's disease (PD). MPTP administered in vivo to mice causes selective loss of dopaminergic neurons in the substantia nigra (SN), as in this disease. Cell death may be induced in vitro by MPP+, the active metabolite of MPTP, when neuronal cell cultures are used. Biochemical mechanisms underlying cell death induced by MPTP/MPP+ still remain to be clarified completely. This article reviews some recent findings linking the effects of MPTP/MPP+ with molecules typically involved in apoptotic pathways. This type of research has made extensive use of genetically manipulated systems such as transgenic mice and transfected cell lines. Evidence has emerged to suggest that Bcl-2, Bax, INK, and caspases are implicated in neurotoxic effects due to in vivo MPTP administration to mice. Different neuronal cell lines such as MN9D cells, SH-SY5Y cells, cerebellar granule neurons, cortical neurons, and GH3 cells were also tested to investigate the possible involvement of Bcl-2, Bax, and caspases in in vitro MPP+-induced neurotoxicity. (C) 2002 Elsevier Science Inc. All rights reserved.