In this review, we provide recent data on the role of mTOR kinase in the brain under physiological conditions and after damage, with a particular focus on cerebral ischemia. We cover the upstream and downstream pathways that regulate the activation state of mTOR complexes. Furthermore, we summarize recent advances in our understanding of mTORC1 and mTORC2 status in ischemia-hypoxia at tissue and cellular levels and analyze the existing evidence related to two types of neural cells, namely glia and neurons. Finally, we discuss the potential use of mTORC1 and mTORC2 as therapeutic targets after stroke.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8911477 | PMC |
| http://dx.doi.org/10.3390/ijms23052814 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The 40S ribosomal subunit recycling complex modulates mitochondrial dynamics and endoplasmic reticulum - mitochondria tethering at mitochondrial fission/fusion hotspots.
Nat Commun
January 2025
Department of Biological Sciences, Dedman College of Humanities and Sciences, Southern Methodist University, Dallas, TX, 75275, USA.
The 40S ribosomal subunit recycling pathway is an integral link in the cellular quality control network, occurring after translational errors have been corrected by the ribosome-associated quality control (RQC) machinery. Despite our understanding of its role, the impact of translation quality control on cellular metabolism remains poorly understood. Here, we reveal a conserved role of the 40S ribosomal subunit recycling (USP10-G3BP1) complex in regulating mitochondrial dynamics and function.
View Article and Find Full Text PDFA novel rapalog shows improved safety vs. efficacy in a human organoid model of polycystic kidney disease.
Stem Cell Reports
January 2025
Department of Medicine, Division of Nephrology, Institute for Stem Cell & Regenerative Medicine, and Kidney Research Institute, University of Washington School of Medicine, Seattle, WA 98109, USA; Plurexa LLC, Seattle, WA 98109, USA. Electronic address:
The mammalian target of rapamycin (mTOR) pathway is a therapeutic target in polycystic kidney disease (PKD), but mTOR inhibitors such as everolimus have failed to show efficacy at tolerated doses in clinical trials. Here, we introduce AV457, a novel rapalog developed to reduce side effects, and assess its dose-dependent safety and efficacy versus everolimus in PKD1 and PKD2 human kidney organoids, which form cysts in a PKD-specific way. Both AV457 and everolimus reduce cyst growth over time.
View Article and Find Full Text PDFmTOR Ser1261 is an AMPK-dependent phosphosite in mouse and human skeletal muscle not required for mTORC2 activity.
FASEB J
January 2025
August Krogh Section for Human and Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark.
The kinases AMPK, and mTOR as part of either mTORC1 or mTORC2, are major orchestrators of cellular growth and metabolism. Phosphorylation of mTOR Ser1261 is reportedly stimulated by both insulin and AMPK activation and a regulator of both mTORC1 and mTORC2 activity. Intrigued by the possibilities that Ser1261 might be a convergence point between insulin and AMPK signaling in skeletal muscle, we investigated the regulation and function of this site using a combination of human exercise, transgenic mouse, and cell culture models.
View Article and Find Full Text PDFSurvival strategies of cancer cells: the role of macropinocytosis in nutrient acquisition, metabolic reprogramming, and therapeutic targeting.
Autophagy
January 2025
Department of General Surgery, Aerospace Center Hospital, Beijing, China.
Macropinocytosis is a nonselective form of endocytosis that allows cancer cells to largely take up the extracellular fluid and its contents, including nutrients, growth factors, etc. We first elaborate meticulously on the process of macropinocytosis. Only by thoroughly understanding this entire process can we devise targeted strategies against it.
View Article and Find Full Text PDFTSC complex decrease the expression of mTOR by regulated miR-199b-3p.
Sci Rep
January 2025
Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Institutes of Biomedical Sciences, Shanxi University, Taiyuan, 030006, China.
The TSC complex formed by TSC1 and TSC2 is the most important upstream negative regulator of mTORC1. Genetic variations in either TSC1 or TSC2 cause tuberous sclerosis complex (TSC) disease which is a rare autosomal dominant disorder resulting in impairment of multiple organ systems. In this study, besides a reported variation, c.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!