摘要
随着我国人口老龄化不断加剧,神经退行性疾病的发病率呈明显上升趋势.神经退行性疾病的主要特征为大脑和脊髓特定神经元的进行性丢失,并伴随认知和运动障碍等神经功能障碍.常见的神经退行性疾病包括阿尔茨海默病(Alzheimer′s disease, AD)、亨廷顿病(Huntington′s disease, HD)、帕金森病(Parkinson′s disease, PD)和肌萎缩侧索硬化症(amyotrophic lateral sclerosis, ALS)等.近年来的研究表明,生长停滞和DNA损伤诱导蛋白34(growth arrest and DNA damage-inducible protein 34,GADD34)与神经退行性疾病密切相关.GADD34是蛋白磷酸酶1(protein phosphatase 1,PP1)的调节亚基,当细胞受到氧化应激、内质网应激和病毒感染等压力时被诱导表达,从而促进细胞的压力适应以及稳态恢复.然而,GADD34在神经退行性疾病患者及小鼠模型中表达异常,并在其病理发生过程中发挥重要作用.因此,GADD34将有望成为治疗神经退行性疾病的潜在新靶点.
With the aging of China′s population,the incidence of neurodegenerative diseases has been increasing significantly.Neurodegenerative diseases were characterized by the gradual loss of specific neurons in cerebrum and spinal cord,concomitantly with neurological dysfunction,such as cognitive impairment and movement disorder.Common neurodegenerative diseases included Alzheimer′s disease(AD),Huntington′s disease(HD),Parkinson′s disease(PD),and amyotrophic lateral sclerosis(ALS).Recent studies showed that growth arrest and DNA damage-inducible protein 34(GADD34)was closely associated with neurodegenerative diseases.As a regulatory subunit of protein phosphatase 1(PP1),GADD34 was induced when cells were exposed to oxidative stress,endoplasmic reticulum stress,viral infection and other stress.GADD34 played an important role in cellular adaptation to stress and homeostasis restoration.However,GADD34 was aberrantly expressed in patients and mouse models of neurodegenerative diseases,which was essential for the pathogenesis of neurodegenerative diseases.Consequently,GADD34 was expected to be a potential target for treatment of neurodegenerative diseases.The role of GADD34 in neurodegenerative diseases was also briefly summarized and discussed.
作者
金志刚
管观文
顾锦瑄
陈俊熠
JIN Zhigang;GUAN Guanwen;GU Jinxuan;CHEN Junyi(College of Life Sciences,Zhejiang Normal University,Jinhua 321004,China)
出处
《浙江师范大学学报（自然科学版）》
CAS
2024年第2期121-132,共12页
Journal of Zhejiang Normal University:Natural Sciences
基金
国家自然科学基金资助项目(31970755)
浙江省自然科学基金资助项目(LY21C120001)。
作者简介
金志刚(1976—),男,江苏苏州人,教授,博士.研究方向:细胞应激反应及其相关疾。
