Dual roles of UPRer and UPRmt in neurodegenerative diseases

doi:10.1007/s00109-023-02382-9

Review

. 2023 Dec;101(12):1499-1512.

doi: 10.1007/s00109-023-02382-9. Epub 2023 Oct 10.

Dual roles of UPR^er and UPR^mt in neurodegenerative diseases

Si Xu¹, Haihui Liu¹, Chen Wang¹, Yu Deng¹, Bin Xu¹, Tianyao Yang², Wei Liu³

Affiliations

¹ Department of Environmental Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenbei New District, Shenyang 110122, Liaoning, China.
² Department of Environmental Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenbei New District, Shenyang 110122, Liaoning, China. tyyang@cmu.edu.cn.
³ Department of Environmental Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenbei New District, Shenyang 110122, Liaoning, China. liuw@cmu.edu.cn.

PMID: 37817014
DOI: 10.1007/s00109-023-02382-9

Review

Dual roles of UPR^er and UPR^mt in neurodegenerative diseases

Si Xu et al. J Mol Med (Berl). 2023 Dec.

. 2023 Dec;101(12):1499-1512.

doi: 10.1007/s00109-023-02382-9. Epub 2023 Oct 10.

Authors

Si Xu¹, Haihui Liu¹, Chen Wang¹, Yu Deng¹, Bin Xu¹, Tianyao Yang², Wei Liu³

Affiliations

¹ Department of Environmental Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenbei New District, Shenyang 110122, Liaoning, China.
² Department of Environmental Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenbei New District, Shenyang 110122, Liaoning, China. tyyang@cmu.edu.cn.
³ Department of Environmental Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenbei New District, Shenyang 110122, Liaoning, China. liuw@cmu.edu.cn.

PMID: 37817014
DOI: 10.1007/s00109-023-02382-9

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 (UPR^er) and the mitochondrial unfolded protein response (UPR^mt) in the development of several neurodegenerative diseases.

Keywords: Endoplasmic reticulum; Mitochondrion; Neurodegenerative diseases; Unfolded protein responses.

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Cited by

Comprehensive Overview of Alzheimer's Disease: Etiological Insights and Degradation Strategies.
Singh MK, Shin Y, Ju S, Han S, Kim SS, Kang I. Singh MK, et al. Int J Mol Sci. 2024 Jun 24;25(13):6901. doi: 10.3390/ijms25136901. Int J Mol Sci. 2024. PMID: 39000011 Free PMC article. Review.

References

1. Hetz C, Chevet E, Oakes SA (2015) Proteostasis control by the unfolded protein response. Nat Cell Biol 17(7):829–838. https://doi.org/10.1038/ncb3184 - DOI - PubMed - PMC
1. Fiorese CJ, Haynes CM (2017) Integrating the UPR(mt) into the mitochondrial maintenance network. Crit Rev Biochem Mol Biol 52(3):304–313. https://doi.org/10.1080/10409238.2017.1291577 - DOI - PubMed - PMC
1. Dugger BN, Dickson DW (2017) Pathology of neurodegenerative diseases. Cold Spring Harb Perspect Biol 9(7). https://doi.org/10.1101/cshperspect.a028035
1. Vincenz-Donnelly L, Hipp MS (2017) The endoplasmic reticulum: a hub of protein quality control in health and disease. Free Radical Biol Med 108:383–393. https://doi.org/10.1016/j.freeradbiomed.2017.03.031 - DOI
1. Fregno I, Molinari M (2019) Proteasomal and lysosomal clearance of faulty secretory proteins: ER-associated degradation (ERAD) and ER-to-lysosome-associated degradation (ERLAD) pathways. Crit Rev Biochem Mol Biol 54(2):153–163. https://doi.org/10.1080/10409238.2019.1610351 - DOI - PubMed

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[1] Hetz C, Chevet E, Oakes SA (2015) Proteostasis control by the unfolded protein response. Nat Cell Biol 17(7):829–838. https://doi.org/10.1038/ncb3184 - DOI - PubMed - PMC

[2] Hetz C, Chevet E, Oakes SA (2015) Proteostasis control by the unfolded protein response. Nat Cell Biol 17(7):829–838. https://doi.org/10.1038/ncb3184 - DOI - PubMed - PMC

[3] Fiorese CJ, Haynes CM (2017) Integrating the UPR(mt) into the mitochondrial maintenance network. Crit Rev Biochem Mol Biol 52(3):304–313. https://doi.org/10.1080/10409238.2017.1291577 - DOI - PubMed - PMC

[4] Fiorese CJ, Haynes CM (2017) Integrating the UPR(mt) into the mitochondrial maintenance network. Crit Rev Biochem Mol Biol 52(3):304–313. https://doi.org/10.1080/10409238.2017.1291577 - DOI - PubMed - PMC

[5] Dugger BN, Dickson DW (2017) Pathology of neurodegenerative diseases. Cold Spring Harb Perspect Biol 9(7). https://doi.org/10.1101/cshperspect.a028035

[6] Dugger BN, Dickson DW (2017) Pathology of neurodegenerative diseases. Cold Spring Harb Perspect Biol 9(7). https://doi.org/10.1101/cshperspect.a028035

[7] Vincenz-Donnelly L, Hipp MS (2017) The endoplasmic reticulum: a hub of protein quality control in health and disease. Free Radical Biol Med 108:383–393. https://doi.org/10.1016/j.freeradbiomed.2017.03.031 - DOI

[8] Vincenz-Donnelly L, Hipp MS (2017) The endoplasmic reticulum: a hub of protein quality control in health and disease. Free Radical Biol Med 108:383–393. https://doi.org/10.1016/j.freeradbiomed.2017.03.031 - DOI

[9] Fregno I, Molinari M (2019) Proteasomal and lysosomal clearance of faulty secretory proteins: ER-associated degradation (ERAD) and ER-to-lysosome-associated degradation (ERLAD) pathways. Crit Rev Biochem Mol Biol 54(2):153–163. https://doi.org/10.1080/10409238.2019.1610351 - DOI - PubMed

[10] Fregno I, Molinari M (2019) Proteasomal and lysosomal clearance of faulty secretory proteins: ER-associated degradation (ERAD) and ER-to-lysosome-associated degradation (ERLAD) pathways. Crit Rev Biochem Mol Biol 54(2):153–163. https://doi.org/10.1080/10409238.2019.1610351 - DOI - PubMed

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Dual roles of UPR^er and UPR^mt in neurodegenerative diseases

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Dual roles of UPR^er and UPR^mt in neurodegenerative diseases

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