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The role of endoplasmic reticulum stress in neurodegenerative disease

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Abstract

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.

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Acknowledgments

This work was supported by two Grants from the China National Natural Science Foundation (No. 81571324) and Education Department of LiaoNing Province, China (No. LJQ2014083).

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    1. PTSD laboratory, Department of Histology and Embryology, Basic Medical University, China Medical University, No. 77, PuHe Road, ShenBei New District, Shenyang, 110122, China

      Chunchen Xiang, Yujia Wang, Han Zhang & Fang Han

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    Chunchen Xiang, Yujia Wang and Han Zhang contributed equally.

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    Xiang, C., Wang, Y., Zhang, H. et al. The role of endoplasmic reticulum stress in neurodegenerative disease. Apoptosis 22, 1–26 (2017). https://doi.org/10.1007/s10495-016-1296-4

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