Mechanisms underlying neural cell death in neurodegenerative diseases: alterations of a developmentally-mediated cellular rheostat
Mechanisms underlying neural cell death in neurodegenerative diseases: alterations of a developmentally-mediated cellular rheostat
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DOI：
10.1016/s0166-2236(00)01705-7
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发表时间：
2000-12-01
影响因子：
15.9
通讯作者：
Gokhan, S
中科院分区：
文献类型：
--
作者：
Mehler, MF;Gokhan, S
与神经退行性疾病相关的基因通常在整个神经发育过程中表达，并且对于神经元亚群的精心制作和维持是必不可少的。致病突变可以以微妙的方式损害这些神经特化事件的限定子集，其最初导致进化的区域神经元亚群的细胞稳态的损害，以及来自正常非致死性环境应激源的成年发作细胞死亡，因此，神经退行性疾病可能代表一类新出现的发育障碍，其特征在于对亚阈值神经发育异常的新生物学反应，这些异常损害靶向神经元生物合成途径而不引起明显的发育缺陷。这种发病机制的发展模型预测，它将很快有可能确定这些功能障碍的途径之前发生的不可逆的细胞损伤，并成功地干预使用创新的神经保护和神经再生策略。
Genes associated with neurodegenerative diseases are normally expressed throughout neural development and are essential for the elaboration and maintenance of neuronal subpopulations, Disease-causing mutations can compromise defined subsets of these neural specification events in subtle ways that initially lead to impairments in the cellular homeostasis of evolving regional neuronal subpopulations, and adult-onset cell death from normally non-lethal environmental stressors, Neurodegenerative diseases may, therefore, represent an emerging class of developmental disorders characterized by novel biological responses to subthreshold neurodevelopmental abnormalities that impair targeted neuronal biosynthetic pathways without causing obvious developmental deficits. This developmental model of pathogenesis predicts that it will soon be possible to identify these dysfunctional pathways prior to the occurrence of irreversible cellular injury, and to successfully intervene using innovative neuroprotective and neural regenerative strategies.