Vall d'Hebron Research Institute-CIBERNED, Barcelona, Spain.
Antioxid Redox Signal. 2012 May 1;16(9):883-95. doi: 10.1089/ars.2011.4074. Epub 2011 Jul 18.
Abstract Significance: Activation of mitochondrion-dependent programmed cell death (PCD) pathways is instrumental to the demise of substantia nigra pars compacta dopaminergic neurons in experimental mouse models of Parkinson's disease (PD). Supporting the relevance of these findings for PD, key molecular elements of this pathogenic cascade have also been demonstrated in postmortem brain samples of PD patients. Recent Advances and Critical Issues: Mounting evidence indicates that different morphological types of cell death co-exist in the brain of PD patients, all of which may result from the activation of common upstream PCD pathways. Indeed, contrary to initial views, it is now established that the deleterious effects of PCD pathways are not limited to mitochondrion-mediated caspase-dependent apoptosis but also involve caspase-independent nonapoptotic cell death, including necrosis. This notion may help reconcile the observation of both apoptotic and nonapoptotic dopaminergic cell death in postmortem PD samples.
Potential neuroprotective strategies for PD should be aimed at targeting both apoptotic and nonapoptotic pathways, all of which may simultaneously occur in PD patients through activation of common upstream PCD pathways involving the mitochondria. Antioxid. Redox Signal. 16, 883-895.
抽象意义：线粒体依赖性程序性细胞死亡（PCD）途径的激活对于实验性帕金森病（PD）小鼠模型中黑质致密部多巴胺能神经元的死亡至关重要。支持这些发现与 PD 的相关性，该致病级联的关键分子元素也在 PD 患者的死后脑组织样本中得到了证实。新进展和关键问题：越来越多的证据表明，不同形态类型的细胞死亡共存于 PD 患者的大脑中，所有这些可能都源于共同的上游 PCD 途径的激活。事实上，与最初的观点相反，现在已经确定 PCD 途径的有害影响不仅限于线粒体介导的半胱天冬酶依赖性细胞凋亡，还包括半胱天冬酶非依赖性非凋亡性细胞死亡，包括坏死。这一概念可能有助于解释在 PD 死后样本中观察到的凋亡和非凋亡性多巴胺能细胞死亡。
PD 的潜在神经保护策略应该旨在针对凋亡和非凋亡途径，所有这些途径都可能通过激活涉及线粒体的共同上游 PCD 途径同时发生在 PD 患者中。抗氧化。氧化还原信号。16,883-895。
