TY - JOUR
T1 - mTOR/AMPK signaling in the brain
T2 - Cell metabolism, proteostasis and survival
AU - Garza-Lombó, Carla
AU - Schroder, Annika
AU - Reyes-Reyes, Elsa M.
AU - Franco, Rodrigo
N1 - Funding Information:
This work was supported by the National Institutes of Health Grant P20RR17675 Centers of Biomedical Research Excellence (COBRE) , the Research Council of the University of Nebraska-Lincoln (R.F.), the National Science Foundation Grant DBI-1461240 (R.F. and A.S.), and the University of Arizona Diversity and Inclusion Award and Career Development Award (EMRR). PhD fellowship for CG-L (290116) was provided by CONACYT. This work was performed in partial fulfillment of the requirements for the PhD degree of CG-L in the posgrado en Ciencias Biomédicas at the Universidad Nacional Autónoma de México.
Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/4
Y1 - 2018/4
N2 - The mechanistic (or mammalian) target of rapamycin (mTOR) and the adenosine monophosphate-activated protein kinase (AMPK) regulate cell survival and metabolism in response to diverse stimuli such as variations in amino acid content, changes in cellular bioenergetics, oxygen levels, neurotrophic factors and xenobiotics. This Opinion paper aims to discuss the current state of knowledge regarding how mTOR and AMPK regulate the metabolism and survival of brain cells and the close interrelationship between both signaling cascades. It is now clear that both mTOR and AMPK pathways regulate cellular homeostasis at multiple levels. Studies so far demonstrate that dysregulation in these two pathways is associated with neuronal injury, degeneration and neurotoxicity, but the mechanisms involved remain unclear. Most of the work so far has been focused on their antagonistic regulation of autophagy, but recent findings highlight that changes in protein synthesis, metabolism and mitochondrial function are likely to play a role in the regulatory effects of both mTOR and AMPK on neuronal health. Understanding their role and relationship between these two master regulators of cell metabolism is crucial for future therapeutic approaches to counteract alterations in cell metabolism and survival in brain injury and disease.
AB - The mechanistic (or mammalian) target of rapamycin (mTOR) and the adenosine monophosphate-activated protein kinase (AMPK) regulate cell survival and metabolism in response to diverse stimuli such as variations in amino acid content, changes in cellular bioenergetics, oxygen levels, neurotrophic factors and xenobiotics. This Opinion paper aims to discuss the current state of knowledge regarding how mTOR and AMPK regulate the metabolism and survival of brain cells and the close interrelationship between both signaling cascades. It is now clear that both mTOR and AMPK pathways regulate cellular homeostasis at multiple levels. Studies so far demonstrate that dysregulation in these two pathways is associated with neuronal injury, degeneration and neurotoxicity, but the mechanisms involved remain unclear. Most of the work so far has been focused on their antagonistic regulation of autophagy, but recent findings highlight that changes in protein synthesis, metabolism and mitochondrial function are likely to play a role in the regulatory effects of both mTOR and AMPK on neuronal health. Understanding their role and relationship between these two master regulators of cell metabolism is crucial for future therapeutic approaches to counteract alterations in cell metabolism and survival in brain injury and disease.
KW - Adenosine monophosphate-activated protein kinase
KW - Autophagy
KW - Cell death
KW - Energy failure
KW - Glycolysis
KW - Mammalian target of rapamycin
KW - Mitochondria
KW - Nutrient deprivation
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U2 - 10.1016/j.cotox.2018.05.002
DO - 10.1016/j.cotox.2018.05.002
M3 - Review article
C2 - 30417160
AN - SCOPUS:85048471592
VL - 8
SP - 102
EP - 110
JO - Current Opinion in Toxicology
JF - Current Opinion in Toxicology
SN - 2468-2020
ER -