2. Materiali e Metodi
3.11 Conclusioni (II parte, modello infiammato)
Le cellule di microglia umana C20 e HMC3:
▪ Aumentano l’espressione dei membri chiave del transduceosoma e metabolone.
▪ L’analisi di predizione dei siti di legame per fattori di trascrizione nella sequenza del promotore di CYP11A1 ha indicato la presenza di matrici per fattori di trascrizione implicati nella regolazione dell’espressione di proteine coinvolte nei processi infiammatori, quali AP-1, STAT5, RORA, PPARγ e Nur77.
▪ Oltre ad aumentare i trascritti per gli enzimi della cascata neurosteroidogenica, che già in condizioni basali risultavano espressi ad alti livelli, aumentano anche altri enzimi, quali il sistema 5β-RED/3α-HSD nelle cellule C20 e l’aromatasi in entrambi i tipi cellulari.
4.Conclusioni finali
I dati ottenuti nella presente tesi mediante l’impiego di due modelli in vitro di microglia primaria hanno permesso di approfondire la nostra conoscenza sulle attività della microglia umana, con particolare riferimento alla neurosteroidogenesi. In particolare, in condizioni basali, hanno dimostrano l’espressione costitutiva di StAR, membro chiave del transduceosoma, nonchè di trascritti di enzimi della cascata neurosteroidogenica implicati nella produzione di molecole steroidee notoriamente implicati nella modulazione di attività del SNC. Il protagonista della modulazione dell’attività neurosteroidogenica basale della microglia è risultato essere TSPO, che è espresso costitutivamente già ad alti livelli nella microglia. Nella microglia reattiva si è riscontrato l’aumento di tutti i membri del transduceosoma/metabolone e di trascritti codificanti gli enzimi della cascata neurosteroidogenica, indicando un ruolo importante delle molecole steroidee nella modulazione del fenotipo infiammato. In modo importante, la valutazione di fattori neurotrofici come BDNF, la cui attività sembra essere mediata dai neurosteroidi, apre la strada a nuove possibili strategie terapeutiche mirate alla neuroprotezione.
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Ringraziamenti
Vorrei ringraziare la mia famiglia e miei amici più cari che mi hanno supportato durante questi anni di studio universitario. Inoltre ringrazio la professoressa Barbara Costa e il dottor Lorenzo Germelli per la supervisione nella realizzazione di questo progetto di tesi.
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