Relationship Between ER Stress and CFTR Gene and Its Role in Alzheimer's Disease

Research Article
Open access

Relationship Between ER Stress and CFTR Gene and Its Role in Alzheimer's Disease

Jiatong Chen 1*
  • 1 Hangzhou Entel Foreign Language School, Hangzhou, 311122, China    
  • *corresponding author 1843261966@qq.com
Published on 20 June 2025 | https://doi.org/10.54254/2753-8818/2025.24216
TNS Vol.116
ISSN (Print): 2753-8826
ISSN (Online): 2753-8818
ISBN (Print): 978-1-80590-197-6
ISBN (Online): 978-1-80590-198-3

Abstract

This research proposal aims to study the relationship between CFTR gene and ER stress and its potential involvement in the aetiology of AD. Using CRISPR Cas9 technology, we intend to induce the F508del mutation in the CFTR gene of a mouse model in a way that mimics the pathophysiological state of Cystic Fibrosis. It describes a study design, including the assessment of spatial learning capability in the Morris Water Maze experiment, and the analysis of Aβ protein aggregation in the hippocampus. The results may give clues as to the molecular mechanisms of Alzheimer's disease and help identify new targets for therapeutic intervention.

Keywords:

Endoplasmic Reticulum stress, CFTR gene, Alzheimer's disease, Unfolded Protein Response, CRISPR-Cas9

Chen,J. (2025). Relationship Between ER Stress and CFTR Gene and Its Role in Alzheimer's Disease. Theoretical and Natural Science,116,57-62.
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References

[1]. Schwarz D.S., Blower M.D. The endoplasmic reticulum: Structure, function and response to cellular signaling. Cell. Mol. Life Sci. 2016;73:79–94. doi: 10.1007/s00018-015-2052-6

[2]. Lopata A, Kniss A, Löhr F, Rogov VV, Dötsch V. Ubiquitination in the ERAD Process. Int J Mol Sci. 2020 Jul 28;21(15):5369. doi: 10.3390/ijms21155369. PMID: 32731622; PMCID: PMC7432864.

[3]. Zou L, Wang X, Zhao F, Wu K, Li X, Li Z, Li Y, Chen W, Zeng S, Liu X, Zhao M, Yi L, Fan S, Chen J. Viruses Hijack ERAD to Regulate Their Replication and Propagation. Int J Mol Sci. 2022 Aug 20;23(16):9398. doi: 10.3390/ijms23169398. PMID: 36012666; PMCID: PMC9408921.

[4]. Anderson NS, Haynes CM. Folding the Mitochondrial UPR into the Integrated Stress Response. Trends Cell Biol. 2020 Jun;30(6):428-439. doi: 10.1016/j.tcb.2020.03.001. Epub 2020 Apr 2. PMID: 32413314; PMCID: PMC7230072.

[5]. Carrara M., Prischi F., Nowak P.R., Kopp M.C., Ali M.M.U. Noncanonical binding of BiP ATPase domain to Ire1 and Perk is dissociated by unfolded protein CH1 to initiate ER stress signaling. Elife. 2015;4:e03522. doi: 10.7554/eLife.03522.

[6]. Ghemrawi, R., & Khair, M. (2020). Endoplasmic Reticulum Stress and Unfolded Protein Response in Neurodegenerative Diseases. International Journal of Molecular Sciences, 21(17). https://doi.org/10.3390/ijms21176127

[7]. Dean, M., Santis, G. Heterogeneity in the severity of cystic fibrosis and the role of CFTR gene mutations. Hum Genet 93, 364–368 (1994). https://doi.org/10.1007/BF00201659

[8]. C. Bareil, A. Bergougnoux. CFTR gene variants, epidemiology and molecular pathology. Archives de Pédiatrie, 2020, 27, pp.eS8-eS12. ⟨10.1016/S0929-693X(20)30044-0⟩. ⟨hal-03477908⟩

[9]. Lopes-Pacheco M. CFTR Modulators: The Changing Face of Cystic Fibrosis in the Era of Precision Medicine. Front Pharmacol. 2020 Feb 21;10:1662. doi: 10.3389/fphar.2019.01662. PMID: 32153386; PMCID: PMC7046560.

[10]. McDonald EF, Meiler J, Plate L. CFTR Folding: From Structure and Proteostasis to Cystic Fibrosis Personalized Medicine. ACS Chem Biol. 2023 Oct 20;18(10):2128-2143. doi: 10.1021/acschembio.3c00310. Epub 2023 Sep 20. PMID: 37730207; PMCID: PMC10595991.

Cite this article

Chen,J. (2025). Relationship Between ER Stress and CFTR Gene and Its Role in Alzheimer's Disease. Theoretical and Natural Science,116,57-62.

Data availability

The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.

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About volume

Volume title: Proceedings of the 3rd International Conference on Modern Medicine and Global Health

ISBN：978-1-80590-197-6(Print) / 978-1-80590-198-3(Online)
Editor：Sheiladevi Sukumaran
Conference website: https://2025.icmmgh.org/
Conference date: 20 January 2025
Series: Theoretical and Natural Science
Volume number: Vol.116
ISSN：2753-8818(Print) / 2753-8826(Online)

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References

[1]. Schwarz D.S., Blower M.D. The endoplasmic reticulum: Structure, function and response to cellular signaling. Cell. Mol. Life Sci. 2016;73:79–94. doi: 10.1007/s00018-015-2052-6

[2]. Lopata A, Kniss A, Löhr F, Rogov VV, Dötsch V. Ubiquitination in the ERAD Process. Int J Mol Sci. 2020 Jul 28;21(15):5369. doi: 10.3390/ijms21155369. PMID: 32731622; PMCID: PMC7432864.

[3]. Zou L, Wang X, Zhao F, Wu K, Li X, Li Z, Li Y, Chen W, Zeng S, Liu X, Zhao M, Yi L, Fan S, Chen J. Viruses Hijack ERAD to Regulate Their Replication and Propagation. Int J Mol Sci. 2022 Aug 20;23(16):9398. doi: 10.3390/ijms23169398. PMID: 36012666; PMCID: PMC9408921.

[4]. Anderson NS, Haynes CM. Folding the Mitochondrial UPR into the Integrated Stress Response. Trends Cell Biol. 2020 Jun;30(6):428-439. doi: 10.1016/j.tcb.2020.03.001. Epub 2020 Apr 2. PMID: 32413314; PMCID: PMC7230072.

[5]. Carrara M., Prischi F., Nowak P.R., Kopp M.C., Ali M.M.U. Noncanonical binding of BiP ATPase domain to Ire1 and Perk is dissociated by unfolded protein CH1 to initiate ER stress signaling. Elife. 2015;4:e03522. doi: 10.7554/eLife.03522.

[6]. Ghemrawi, R., & Khair, M. (2020). Endoplasmic Reticulum Stress and Unfolded Protein Response in Neurodegenerative Diseases. International Journal of Molecular Sciences, 21(17). https://doi.org/10.3390/ijms21176127

[7]. Dean, M., Santis, G. Heterogeneity in the severity of cystic fibrosis and the role of CFTR gene mutations. Hum Genet 93, 364–368 (1994). https://doi.org/10.1007/BF00201659

[8]. C. Bareil, A. Bergougnoux. CFTR gene variants, epidemiology and molecular pathology. Archives de Pédiatrie, 2020, 27, pp.eS8-eS12. ⟨10.1016/S0929-693X(20)30044-0⟩. ⟨hal-03477908⟩

[9]. Lopes-Pacheco M. CFTR Modulators: The Changing Face of Cystic Fibrosis in the Era of Precision Medicine. Front Pharmacol. 2020 Feb 21;10:1662. doi: 10.3389/fphar.2019.01662. PMID: 32153386; PMCID: PMC7046560.

[10]. McDonald EF, Meiler J, Plate L. CFTR Folding: From Structure and Proteostasis to Cystic Fibrosis Personalized Medicine. ACS Chem Biol. 2023 Oct 20;18(10):2128-2143. doi: 10.1021/acschembio.3c00310. Epub 2023 Sep 20. PMID: 37730207; PMCID: PMC10595991.

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