A multi‐organ analysis of the role of mTOR in fetal alcohol spectrum disorders
Open Access
- 31 March 2023
- journal article
- review article
- Published by Wiley in The FASEB Journal
- Vol. 37 (5) , e22897
Abstract
Alcohol exposure during gestation can lead to fetal alcohol spectrum disorders (FASD), an array of cognitive and physical developmental impairments. Over the past two and a half decades, Mammalian Target of Rapamycin (mTOR) has emerged at the nexus of many fields of study, and has recently been implicated in FASD etiology. mTOR plays an integral role in modulating anabolic and catabolic activities, including protein synthesis and autophagy. These processes are vital for proper development and can have long lasting effects following alcohol exposure, such as impaired hippocampal and synapse formation, reduced brain size, as well as cognitive, behavioral, and memory impairments. We highlight recent advances in the field of FASD, primarily with regard to animal model discoveries and discuss the interaction between alcohol and mTOR in the context of various tissues, including brain, placenta, bone, and muscle, with respect to developmental alcohol exposure paradigms. The current review focuses on novel FASD research within the context of the mTOR signaling and sheds light on mechanistic etiologies at various biological levels including molecular, cellular, and functional, across multiple stages of development and illuminates the dichotomy between the different mTOR complexes and their unique signaling roles.Keywords
Funding Information
- National Institute on Alcohol Abuse and Alcoholism (AA23520, AA23035)
This publication has 57 references indexed in Scilit:
- The Transcription Factor TFEB Links mTORC1 Signaling to Transcriptional Control of Lysosome HomeostasisScience Signaling, 2012
- A lysosome‐to‐nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEBThe EMBO Journal, 2012
- Alcohol-Induced Modulation of Rictor and mTORC2 Activity in C2C12 MyoblastsAlcohol, Clinical and Experimental Research, 2011
- AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1Nature Cell Biology, 2011
- mTORC1 Directly Phosphorylates and Regulates Human MAF1Molecular and Cellular Biology, 2010
- Requirement of the mTOR Kinase for the Regulation of Maf1 Phosphorylation and Control of RNA Polymerase III-dependent Transcription in Cancer CellsJournal of Biological Chemistry, 2010
- Common mechanisms of PIKK regulationDNA Repair, 2009
- ULK1·ATG13·FIP200 Complex Mediates mTOR Signaling and Is Essential for AutophagyJournal of Biological Chemistry, 2009
- Nutrient-dependent mTORC1 Association with the ULK1–Atg13–FIP200 Complex Required for AutophagyMolecular Biology of the Cell, 2009
- S6K1- and ßTRCP-Mediated Degradation of PDCD4 Promotes Protein Translation and Cell GrowthScience, 2006