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

• Published in: International journal of molecular sciences Vol. 21; no. 15; p. 5301
• Main Authors: Rios-Fuller, Tiffany J, Mahe, Melanie, Walters, Beth, Abbadi, Dounia, Pérez-Baos, Sandra, Gadi, Abhilash, Andrews, John J, Katsara, Olga, Vincent, C Theresa, Schneider, Robert J
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26.07.2020; MDPI
• Subjects: Alzheimer's disease; Biosynthesis; Blood pressure; Chronic obstructive pulmonary disease; Cirrhosis; Coronary artery disease; Diabetes; Diabetes mellitus; Disease; eIF2 stress; Endoplasmic reticulum; Eukaryotic Initiation Factor-2 - metabolism; Gene expression; Growth factors; Heart diseases; Homeostasis; Humans; Initiation factor eIF-2α; Kinases; Liver cirrhosis; Liver diseases; Lung diseases; Mechanistic Target of Rapamycin Complex 1 - metabolism; mTOR signaling; non-communicable diseases; Noncommunicable Diseases; Obstructive lung disease; Parkinson's disease; Pathogenesis; Phosphorylation; Polypeptides; Protein Biosynthesis; Proteins; Rapamycin; Review; Risk analysis; Risk factors; Signal Transduction; Stress response; TOR protein; Transcription; Transfer RNA; Translation; Viral infections; non-communicable diseases; translation; mTOR signaling; eIF2 stress
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21155301

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.