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Translation Regulation by eIF2α Phosphorylation and mTORC1 Signaling Pathways in Non-Communicable Diseases (NCDs)

1
Department of Microbiology, NYU School of Medicine, New York, NY 10016, USA
2
Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, 751 85 Uppsala, Sweden
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(15), 5301; https://doi.org/10.3390/ijms21155301
Received: 18 June 2020 / Revised: 20 July 2020 / Accepted: 22 July 2020 / Published: 26 July 2020
(This article belongs to the Special Issue Protein Synthesis and Disease)
Non-communicable diseases (NCDs) are medical conditions that, by definition, are non-infectious and non-transmissible among people. Much of current NCDs are generally due to genetic, behavioral, and metabolic risk factors that often include excessive alcohol consumption, smoking, obesity, and untreated elevated blood pressure, and share many common signal transduction pathways. Alterations in cell and physiological signaling and transcriptional control pathways have been well studied in several human NCDs, but these same pathways also regulate expression and function of the protein synthetic machinery and mRNA translation which have been less well investigated. Alterations in expression of specific translation factors, and disruption of canonical mRNA translational regulation, both contribute to the pathology of many NCDs. The two most common pathological alterations that contribute to NCDs discussed in this review will be the regulation of eukaryotic initiation factor 2 (eIF2) by the integrated stress response (ISR) and the mammalian target of rapamycin complex 1 (mTORC1) pathways. Both pathways integrally connect mRNA translation activity to external and internal physiological stimuli. Here, we review the role of ISR control of eIF2 activity and mTORC1 control of cap-mediated mRNA translation in some common NCDs, including Alzheimer’s disease, Parkinson’s disease, stroke, diabetes mellitus, liver cirrhosis, chronic obstructive pulmonary disease (COPD), and cardiac diseases. Our goal is to provide insights that further the understanding as to the important role of translational regulation in the pathogenesis of these diseases. View Full-Text
Keywords: translation; non-communicable diseases; eIF2 stress; mTOR signaling translation; non-communicable diseases; eIF2 stress; mTOR signaling
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MDPI and ACS Style

Rios-Fuller, T.J.; Mahe, M.; Walters, B.; Abbadi, D.; Pérez-Baos, S.; Gadi, A.; Andrews, J.J.; Katsara, O.; Vincent, C.T.; Schneider, R.J. Translation Regulation by eIF2α Phosphorylation and mTORC1 Signaling Pathways in Non-Communicable Diseases (NCDs). Int. J. Mol. Sci. 2020, 21, 5301. https://doi.org/10.3390/ijms21155301

AMA Style

Rios-Fuller TJ, Mahe M, Walters B, Abbadi D, Pérez-Baos S, Gadi A, Andrews JJ, Katsara O, Vincent CT, Schneider RJ. Translation Regulation by eIF2α Phosphorylation and mTORC1 Signaling Pathways in Non-Communicable Diseases (NCDs). International Journal of Molecular Sciences. 2020; 21(15):5301. https://doi.org/10.3390/ijms21155301

Chicago/Turabian Style

Rios-Fuller, Tiffany J.; Mahe, Melanie; Walters, Beth; Abbadi, Dounia; Pérez-Baos, Sandra; Gadi, Abhilash; Andrews, John J.; Katsara, Olga; Vincent, C. T.; Schneider, Robert J. 2020. "Translation Regulation by eIF2α Phosphorylation and mTORC1 Signaling Pathways in Non-Communicable Diseases (NCDs)" Int. J. Mol. Sci. 21, no. 15: 5301. https://doi.org/10.3390/ijms21155301

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