Janus C
Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL 32224, USA.
Genes Brain Behav. 2008 Feb;7 Suppl 1:12-27. doi: 10.1111/j.1601-183X.2007.00375.x.
Neuronal cell death underlies the majority of age-related human neurodegenerative disorders that culminate with salient and severe cognitive decline affecting patients' quality of life, identity and eventually leading to death. The identification of disease-causing genes in familial forms of neurodegenerative diseases enabled the development of genetic models closely replicating pathologies found in human central nervous system. These models dramatically precipitated our understanding of molecular events leading to neuronal death in many neurodegenerative disorders. Today's large range of cellular and animal models generate rapidly accumulating biochemical and neuropathological data on changes induced by mutated or dysfunctional proteins implicated in neuronal loss. Most of these models are complementary, although all have intrinsic limitations as well as specific advantages. Development of conditional transgenic mouse models in which a deleterious effect of a transgene can be regulated in a controlled way created new possibilities of addressing the basic mechanisms of neurodegeneration and provided a new angle for the development and testing of new therapeutic approaches.
神经元细胞死亡是大多数与年龄相关的人类神经退行性疾病的基础，这些疾病最终会导致显著且严重的认知衰退，影响患者的生活质量、身份认同，并最终导致死亡。在神经退行性疾病的家族形式中鉴定致病基因，使得能够开发出紧密复制人类中枢神经系统中发现的病理状况的遗传模型。这些模型极大地促进了我们对导致许多神经退行性疾病中神经元死亡的分子事件的理解。如今大量的细胞和动物模型正在快速积累有关由与神经元丧失相关的突变或功能失调蛋白所诱导变化的生化和神经病理学数据。尽管所有这些模型都有内在局限性以及特定优势，但大多数模型是互补的。条件性转基因小鼠模型的开发使得转基因的有害作用能够以可控方式进行调节，为解决神经退行性变的基本机制创造了新的可能性，并为新治疗方法的开发和测试提供了新视角。
