Some notes
“ Although mTOR signaling is essential for proper cellular homeostasis, the aberrant activation of mTOR is potentially associated with a myriad of pathological outcomes, including different types of cancer, metabolic/cardiovascular/pulmonary diseases, and neurodegenerative disorders”
Muscles — too much mTOR for too long bad for muscle health
“ The dysregulation of the mTORC1-autophagy axis in muscles results in the development of diverse muscle diseases. Han et al. emphasized the essential role of balancing mTORC1 and autophagy in energy generation/consumption and macromolecule turnover processes for maintaining the physiological condition of skeletal muscles”
Cardiometabolic —- too much mTOR for too long bad for cardiometabolic health
“ adverse effects of dysregulated mTOR signaling in different cardiometabolic diseases, specifically focusing on obesity, non-alcoholic fatty liver disease, and cardiac remodeling and potential strategies involving PKA/PKG activation or PDE inhibition to fight the disease.”
Hearing — too much mTORC1 is bad for hearing
“ the deleterious effects of the overactivation of mTORC1 and the beneficial role of mTORC2 in hair cells”
Wound healing — need mTOR signaling for wound healing but not too much
“mTOR signaling is critical for physiologic wound healing and pathologic fibrogenesis. Aberrant mTOR signaling influences the development of fibrotic disease by inducing fibroblast proliferation, TGF-β1-induced myofibroblast differentiation, the abnormal accumulation of extracellular matrix (ECM), and collagen production. Due to the anti-proliferative property of rapamycin (mTOR inhibitor, mTORi), rapamycin-eluting stents prevent the neointimal formation of graft coronary arteries and reduce the incidence of restenosis following coronary angioplasty, which is highly effective in reducing the risk of coronary artery disease.”
“ The persistent hyperactivation of mTOR signaling in diabetes exacerbates post-ischemic myocardial injuries due to accelerated cardiomyocyte death with cardiac remodeling and inflammatory responses. Our prior studies reported that a rapamycin treatment at the onset of reperfusion reduces the myocardial infarct size in diabetic mice and rabbits by inhibiting mTORC1, while restoring mTORC2”
High glucose — unregulator of mTOR and damager of mitochondria
“ HG conditions significantly reduce the survival of H9c2 cardiomyoblasts with an increase in the ROS level and mitochondrial fragmentation, as well as the loss of the mitochondrial membrane potential (MMP). ”
“ significant induction of expressions of ET-1/ETA-R/ETB-R as well as mTOR/Raptor/Rictor under HG conditions.”
Anticancer — rapalog is anti cancer (a model only)
“ anti-proliferative effects of TKA001 (rapalog) on human prostate, epithelial, and cervical cancer cells. ”