神经药理学报
神經藥理學報
신경약이학보
Journal of Hebei North University(Medical Edition)
2013年
3期
19-26
,共8页
内质网应激%信号转导通路%帕金森病%葡萄糖调节蛋白78%ATF4-CHOP-Puma
內質網應激%信號轉導通路%帕金森病%葡萄糖調節蛋白78%ATF4-CHOP-Puma
내질망응격%신호전도통로%파금삼병%포도당조절단백78%ATF4-CHOP-Puma
endoplasmic reticulum stress(ERS)%signal transduction pathway%Parkinson’s disease(PD)%glucose regulated protein,78(GRP78)%ATF4-CHOP-Puma
内质网是真核细胞中重要的细胞器之一，与维持细胞稳态关系密切。当缺乏葡萄糖、缺氧、体内钙平衡紊乱或者发生氧化应激时，会引起细胞内未折叠蛋白或错误折叠蛋白的积累，导致内质网应激。帕金森病是一种慢性进行性脑变性疾病，典型的病理变化是黑质纹状体多巴胺能神经细胞变性丢失导致的多巴胺神经递质缺乏。目前对帕金森病的治疗多为缓解症状，但不能阻止疾病的进展。通过对内质网应激中的信号通路的研究发现：在帕金森病的发病过程中，多巴胺能神经元的选择性死亡与内质网应激有关。内质网应激过程中的中心调节因子：葡萄糖调节蛋白78（glucose regulated protein 78，GRP78）及其下游ATF4-CHOP-Puma信号通路与帕金森病的发病过程有密切的联系，本文对GRP78及其下游ATF4-CHOP-Puma信号通路近些年来的研究进展进行综述，以期为帕金森病的治疗提供新的靶点和思路。
內質網是真覈細胞中重要的細胞器之一，與維持細胞穩態關繫密切。噹缺乏葡萄糖、缺氧、體內鈣平衡紊亂或者髮生氧化應激時，會引起細胞內未摺疊蛋白或錯誤摺疊蛋白的積纍，導緻內質網應激。帕金森病是一種慢性進行性腦變性疾病，典型的病理變化是黑質紋狀體多巴胺能神經細胞變性丟失導緻的多巴胺神經遞質缺乏。目前對帕金森病的治療多為緩解癥狀，但不能阻止疾病的進展。通過對內質網應激中的信號通路的研究髮現：在帕金森病的髮病過程中，多巴胺能神經元的選擇性死亡與內質網應激有關。內質網應激過程中的中心調節因子：葡萄糖調節蛋白78（glucose regulated protein 78，GRP78）及其下遊ATF4-CHOP-Puma信號通路與帕金森病的髮病過程有密切的聯繫，本文對GRP78及其下遊ATF4-CHOP-Puma信號通路近些年來的研究進展進行綜述，以期為帕金森病的治療提供新的靶點和思路。
내질망시진핵세포중중요적세포기지일，여유지세포은태관계밀절。당결핍포도당、결양、체내개평형문란혹자발생양화응격시，회인기세포내미절첩단백혹착오절첩단백적적루，도치내질망응격。파금삼병시일충만성진행성뇌변성질병，전형적병리변화시흑질문상체다파알능신경세포변성주실도치적다파알신경체질결핍。목전대파금삼병적치료다위완해증상，단불능조지질병적진전。통과대내질망응격중적신호통로적연구발현：재파금삼병적발병과정중，다파알능신경원적선택성사망여내질망응격유관。내질망응격과정중적중심조절인자：포도당조절단백78（glucose regulated protein 78，GRP78）급기하유ATF4-CHOP-Puma신호통로여파금삼병적발병과정유밀절적련계，본문대GRP78급기하유ATF4-CHOP-Puma신호통로근사년래적연구진전진행종술，이기위파금삼병적치료제공신적파점화사로。
Endoplasmic reticulum is one of the important organelles in eukaryotic cells, and it is closely related to the cellular homeostasis state. Glucose shortage, hypoxia, calcium imbalance and oxidative stress all can lead to the accumulation of unfolded or misfolded proteins in the cells,which will lead to endoplasmic reticulum stress. Parkinson’s disease is a chronic progressive neurodegenerative disease, with the typical pathological changes being the lack of the neurotransmitter dopamine resulting from the degeneration and loss of the dopaminergic nerve cells in the substantia nigra striatum. Current treatments of Parkinson's disease is to relieve the symptoms rather than prevent the progression of the disease. Recent research suggests that the selective death of dopaminergic neurons is associated with endoplasmic reticulum stress in the process of the Parkinson’s disease. The central modulating factors of endoplasmic reticulum stress, i.e. glucose regulated protein 78(GRP78)and the downstream ATF4-CHOP-Puma signaling pathway, are closely linked to the progress of the Parkinson’s disease. This review summarized recent developments of the GRP78 and its downstream ATF4-CHOP-Puma signaling pathways, in the hope of providing information for the potential new targets in the treatment of Parkinson’s disease.
