The role of endoplasmic reticulum stress in neurodegenerative disease.
The endoplasmic reticulum (ER) is an important organelle involved in cellular homeostasis and control of protein quality. Unfolded protein response (UPR) is a cellular response to ER stress and promotes cell survival. Severe or prolonged stress activates apoptosis signaling to trigger cell death. In mammals, the UPR is initiated by three major ER stress sensors, including inositol-requiring transmembrane kinase 1, double-stranded RNA-activated protein kinase-like ER kinase and activating transcription factor 6. UPR dysfunction plays an important role in the pathogenesis of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and Huntington's disease, which is characterized by the accumulation and aggregation of misfolded proteins. ER stress mediates the pathogenesis of psychiatric diseases, such as depression, schizophrenia, sleep fragmentation and post-traumatic stress disorder. The role of UPR in the neuropathology of humans, cell lines and animal models, is established. Therefore, inhibition of specific ER mediators may contribute to the treatment and prevention of neurodegeneration. Preclinical studies have shed light on the potential therapeutic strategies. Here, we will review the evidence of UPR activation in neurodegenerative disorders and psychiatric diseases along with the methodology.
PTSD laboratory, Department of Histology and Embryology, Basic Medical University, China Medical University, No. 77, PuHe Road, ShenBei New District, Shenyang, 110122, China.
Chunchen
C
Xiang
PTSD laboratory, Department of Histology and Embryology, Basic Medical University, China Medical University, No. 77, PuHe Road, ShenBei New District, Shenyang, 110122, China.
Yujia
Y
Wang
PTSD laboratory, Department of Histology and Embryology, Basic Medical University, China Medical University, No. 77, PuHe Road, ShenBei New District, Shenyang, 110122, China.
Han
H
Zhang
PTSD laboratory, Department of Histology and Embryology, Basic Medical University, China Medical University, No. 77, PuHe Road, ShenBei New District, Shenyang, 110122, China. fhan@cmu.edu.cn.
Fang
F
Han
D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000473:pathology; D017209:Apoptosis / Q000235:genetics*; D004721:Endoplasmic Reticulum / Q000235:genetics; D059865:Endoplasmic Reticulum Stress / Q000235:genetics*; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000473:pathology; D010300:Parkinson Disease / Q000235:genetics / Q000473:pathology; D056811:Unfolded Protein Response / Q000235:genetics*
ATF6; Endoplasmic reticulum (ER) stress; IRE1; Neurodegeneration; PERK; Unfolded protein response (UPR)