Apoptotic mechanisms and antiapoptotic therapy in the MPTP model of Parkinson's disease
Apoptotic mechanisms and antiapoptotic therapy in the MPTP model of Parkinson's disease
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DOI：
10.1016/s0378-4274(02)00428-9
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发表时间：
2003-04-04
影响因子：
3.5
通讯作者：
Schulz, JB
中科院分区：
文献类型：
--
作者：
Eberhardt, O;Schulz, JB
1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）模型构成了帕金森病最具特征的毒素范例，忠实地复制了其大部分临床和病理学特征。许多证据表明，在细胞培养中应用1-甲基-4-苯基吡啶鎓（MPP+）或体内应用MPTP后，细胞凋亡对细胞死亡有显著贡献。这适用于凋亡DNA链断裂、JNK途径和半胱天冬酶的激活、Par-4蛋白的诱导以及通过干扰p53、Apaf-1或Bax信号传导而赋予的保护。在MPTP模型中，干预细胞凋亡的上游事件，例如通过抑制JNK途径，提供形态和功能拯救。相反，抑制细胞凋亡的传播和执行阶段，例如通过抑制半胱天冬酶，阻断或延迟细胞死亡，但不能恢复神经元功能。在这个阶段，抗凋亡与神经恢复疗法的组合可能是有希望的。(C)2002爱思唯尔科学爱尔兰有限公司保留所有权利。
The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model constitutes the best-characterized toxin paradigm for Parkinson's disease, faithfully replicating most of its clinical and pathological hallmarks. Many lines of evidence point to a significant contribution of apoptosis to cell death after application of 1-methyl-4-phenylpyridinium (MPP+) in cell culture or MPTP in vivo. This holds true for apoptotic DNA strand breaks, activation of the JNK pathway and caspases, induction of Par-4 protein and the protection conferred by interference with p53, Apaf-1 or Bax signalling. In MPTP models, intervention in upstream events of apoptosis, e.g. by inhibition of the JNK pathway, provides morphological and functional rescue. In contrast, inhibition of the propagation and execution phase of apoptosis, e.g. by inhibition of caspases, blocks or delays cell death but may not recover neuronal function. At this stage, the combination of an anti-apoptotic together with a neurorestorative therapy may be promising. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.