Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson's disease

被引:991
作者
Blum, D
Torch, S
Lambeng, N
Nissou, MF
Benabid, AL
Sadoul, R
Verna, JM
机构
[1] CHU Michallon, INSERM, Unite Mixte, F-38043 Grenoble 9, France
[2] ULB Erasme, Dept Neurosci, Neurophysiol Lab, B-1070 Brussels, Belgium
[3] CEA, TDC, DBMS, F-38054 Grenoble 9, France
[4] Immunol Lab, F-38130 Echirolles, France
[5] CHU Michallon, INSERM U318, F-38043 Grenoble 9, France
关键词
Parkinson's disease; apoptosis; 6-OHDA; MPTP; MPP+; dopamine; animal models;
D O I
10.1016/S0301-0082(01)00003-X
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Parkinson's disease (PD) is a neurodegenerative disorder characterized by a preferential loss of the dopaminergic neurons of the substantia nigra pars compacta. Although the etiology of PD is unknown, major biochemical processes such as oxidative stress and mitochondrial inhibition are largely described. However, despite these findings, the actual therapeutics are essentially symptomatical and are not able to block the degenerative process. Recent histological studies performed on brains from PD patients suggest that nigral cell death could be apoptotic. However. since post-mortem studies do not allow precise determination of the sequence of events leading to this apoptotic cell death, the molecular pathways involved in this process have been essentially studied on experimental models reproducing the human disease. These latter are created by using neurotoxic compounds such as 6-hydroxydopamine (6-OHDA), 1-methyl-1-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP) or dopamine (DA). Extensive study of these models have shown that they mimick, in vitro and in vivo, the histological and or the biochemical characteristics of PD and thus help to define important cellular actors of cell death presumably critical for the nigral degeneration. This review reports recent data concerning the biochemical and molecular apoptotic mechanisms underlying the experimental models of PD and correlates them to the phenomena occurring in human disease. (C) 2001 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:135 / 172
页数:38
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