Neurodegenerative diseases, such as Alzheimer' s disease and Parkinson' s disease,are one category of the main diseases threatening human health. However, the etiology of neurodegenerative diseases is not very clear,but mounting evidence indicates that abnormal protein modification,oxidative stress,neurotrophic deficiency and plasticity change may play a certain role in the development and progression of neurodegenerative diseases. Activating transcription factor 4 (ATF4) is a member of the activating transcription factor family, and its expression is induced in response to various environmental stresses. Moreover,ATF4 regulates downstream genes with different functions through binding with various transcription factors, and participates in physiological processes such as differentiation,metabolism and memory formation. Accumulated evidence show that ATF4 expression is specifically increased in a variety of neurodegenerative diseases,and may involve in neurofibrillary tangles,Tau protein hyperphosphorylation,senile plaque formation by β-amyloid proteins and neuronal death and synaptic dysfunction in the brain, suggesting that ATF4 play a certain role in these diseases.%神经退行性疾病如阿尔茨海默病、帕金森病是威胁人类健康的几种主要疾病之一.目前其病因并不明确,但蛋白质异常修饰、氧化应激、神经营养缺乏及可塑性改变均在神经退行性疾病的发展、进程中发挥一定作用.转录激活因子4(ATF4)是激活转录因子家族成员之一,能感应环境多种应激而增加其表达,且ATF4通过与多种细胞转录因子结合,调控具有不同功能的下游基因,参与分化、代谢、记忆形成等生理过程.有证据显示,ATF4的表达在多种神经退行性疾病中特异性升高,并与神经原纤维缠结,Tau蛋白的过度磷酸化,β淀粉样蛋白老年斑形成以及大脑中神经元死亡和神经突触功能受损有关,提示ATF4在这些疾病中发挥一定作用.
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