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Tesi etd-05032021-133239


Tipo di tesi
Tesi di laurea magistrale
Autore
SANNA, NOEMI
URN
etd-05032021-133239
Titolo
mTOR regulation of autophagy and mitochondriogenesis in Glioblastoma Multiforme
Dipartimento
BIOLOGIA
Corso di studi
NEUROSCIENCE
Relatori
relatore Giorgi, Filippo Sean
Parole chiave
  • autophagy
  • electron microscopy
  • glioblastoma multiforme
  • light microscopy
  • mitochondriogenesis
  • mitophagy
  • mtor
  • rapamycin
Data inizio appello
25/05/2021
Consultabilità
Non consultabile
Data di rilascio
25/05/2091
Riassunto
Glioblastoma Multiforme (GBM) is one of the most severe and frequent brain tumors. It is characterized by a high proliferative rate, heterogeneity and treatment resistance. Thus, the ongoing therapies are not very effective in its treatment and patients present, on average, survival of 14 months after diagnosis. Those features could be related, at least in part, to a dysregulation of the mTOR pathway and subsequent Autophagy inhibition. Autophagy is a cellular mechanism through which unfolded proteins and degenerated organelles are degraded. Its initiation is related to the activation of a protein complex that allows the enwrapping of the material and sends it to lysosomal degradation. In Glioma Stem Cells mTOR up-regulation inhibits the activity of this protein complex suppressing autophagy and promoting cell proliferation and metabolism. Moreover, in parallel with autophagy impairment, was observed also mitochondrial impairment. Thus, the two mechanisms of mitochondrial degradation (Mitophagy) and Mitochondrial Biogenesis, that has been seen to be related one to another, are highly reduced during mTOR overactivation. In this work the effects of Rapamycin, an mTOR inhibitor, were evaluated using in vitro GBM models and, through Electron and Light microscopy techniques, it was assessed mitochondrial number and morphology and it was also evaluated the expression of the proteins involved in autophagy/mitophagy and mitochondrial biogenesis. The obtained findings confirm the possibility to induce Autophagy in GBM, through the mTOR inhibition, and the relationship between Autophagy and Mitochondrial Biogenesis. This may have also potential implications for GBM treatment.
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