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Dual roles of UPRer and UPRmt in neurodegenerative diseases

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Abstract

The unfolded protein response (UPR) is a cellular stress response mechanism induced by the accumulation of unfolded or misfolded proteins. Within the endoplasmic reticulum and mitochondria, a dynamic balance exists between protein folding mechanisms and unfolded protein levels under normal conditions. Disruption of this balance or an accumulation of unfolded proteins in these organelles can result in stress responses and UPR. The UPR restores organelle homeostasis and promotes cell survival by increasing the expression of chaperone proteins, regulating protein quality control systems, and enhancing the protein degradation pathway. However, prolonged or abnormal UPR can also have negative effects, including cell death. Therefore, many diseases, especially neurodegenerative diseases, are associated with UPR dysfunction. Neurodegenerative diseases are characterized by misfolded proteins accumulating and aggregating, and neuronal cells are particularly sensitive to misfolded proteins and are prone to degeneration. Many studies have shown that the UPR plays an important role in the pathogenesis of neurodegenerative diseases. Here, we will discuss the possible contributions of the endoplasmic reticulum unfolded protein response (UPRer) and the mitochondrial unfolded protein response (UPRmt) in the development of several neurodegenerative diseases.

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Funding

This work was supported by the National Natural Science Foundation of China (No. 81502779) and Natural Science Foundation of Liaoning Province, China (No. QN2019030).

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  1. Department of Environmental Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenbei New District, Shenyang 110122, Liaoning, China

    Si Xu, Haihui Liu, Chen Wang, Yu Deng, Bin Xu, Tianyao Yang & Wei Liu

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  2. Haihui Liu
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  3. Chen Wang
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  4. Yu Deng
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  5. Bin Xu
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  6. Tianyao Yang
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  7. Wei Liu
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Contributions

Si Xu conceived and drafted this manuscript. All authors revised and approved the final manuscript.

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Correspondence to Tianyao Yang or Wei Liu.

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Xu, S., Liu, H., Wang, C. et al. Dual roles of UPRer and UPRmt in neurodegenerative diseases. J Mol Med 101, 1499–1512 (2023). https://doi.org/10.1007/s00109-023-02382-9

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