mTOR-Dependent Cell Proliferation in the Brain.
Larisa RyskalinGloria LazzeriMarina FlaibaniFrancesca BiagioniStefano GambardellaAlessandro FratiFrancesco FornaiPublished in: BioMed research international (2017)
The mammalian Target of Rapamycin (mTOR) is a molecular complex equipped with kinase activity which controls cell viability being key in the PI3K/PTEN/Akt pathway. mTOR acts by integrating a number of environmental stimuli to regulate cell growth, proliferation, autophagy, and protein synthesis. These effects are based on the modulation of different metabolic pathways. Upregulation of mTOR associates with various pathological conditions, such as obesity, neurodegeneration, and brain tumors. This is the case of high-grade gliomas with a high propensity to proliferation and tissue invasion. Glioblastoma Multiforme (GBM) is a WHO grade IV malignant, aggressive, and lethal glioma. To date, a few treatments are available although the outcome of GBM patients remains poor. Experimental and pathological findings suggest that mTOR upregulation plays a major role in determining an aggressive phenotype, thus determining relapse and chemoresistance. Among several activities, mTOR-induced autophagy suppression is key in GBM malignancy. In this article, we discuss recent evidence about mTOR signaling and its role in normal brain development and pathological conditions, with a special emphasis on its role in GBM.
Keyphrases
- cell proliferation
- signaling pathway
- high grade
- cell cycle
- pi k akt
- end stage renal disease
- oxidative stress
- metabolic syndrome
- white matter
- endoplasmic reticulum stress
- weight loss
- resting state
- multiple sclerosis
- prognostic factors
- ejection fraction
- newly diagnosed
- functional connectivity
- chronic kidney disease
- peritoneal dialysis
- low grade
- body mass index
- skeletal muscle
- brain injury
- long non coding rna
- protein kinase
- human health