Michel P P, Lambeng N, Ruberg M
Institut National de la Santé et de la Recherche Médicale U.289, Hôpital de la Salpêtrière, Paris, France.
Clin Neuropharmacol. 1999 May-Jun;22(3):137-50.
The cause of neuronal death in Parkinson's, Alzheimer's, and other neurodegenerative diseases is not known, except in some hereditary forms of these disorders in which a mutated gene has been identified. Even in these cases, the molecular mechanisms that underlie the loss of specific populations of neurons have not been determined, although it is highly probable that apoptosis is involved. Some of the biochemical events that occur during apoptosis have been elucidated. We focus in this review on the role played by the proapoptotic caspases, the antiapoptotic proteins of the Bcl-2 family, and the apoptosis associated signal transducers such as ceramide, calcium, and reactive nitrogen or oxygen species. The role of the mitochondria and the possible implication of cell cycle regulators will also be addressed. Of particular interest are the endogenous inhibitory mechanisms and the pharmacologic agents that can be used to block apoptosis signaling cascades, because they offer models for the development of therapeutic strategies designed to prevent the evolution of pathologic neurodegeneration.
帕金森病、阿尔茨海默病及其他神经退行性疾病中神经元死亡的原因尚不清楚，但某些遗传性形式的这些疾病除外，在这些疾病中已鉴定出突变基因。即便在这些情况下，尽管很可能涉及细胞凋亡，但导致特定神经元群体丧失的分子机制仍未确定。细胞凋亡过程中发生的一些生化事件已得到阐明。在本综述中，我们重点关注促凋亡半胱天冬酶、Bcl-2家族的抗凋亡蛋白以及与细胞凋亡相关的信号转导分子（如神经酰胺、钙、活性氮或氧物种）所起的作用。线粒体的作用以及细胞周期调节因子的可能影响也将予以探讨。特别令人感兴趣的是内源性抑制机制以及可用于阻断细胞凋亡信号级联反应的药物，因为它们为开发旨在预防病理性神经退行性变进展的治疗策略提供了模型。
