Neuroprotection against myelin disorders: in vitro and in vivo studies to explore the protective roles of TSPO ligands and genome editing-based strategies

In the CNS, the oligodendrocytes (OLs) produce myelin, the lipophilic structure which allows for the proper conduction of nerve impulses. Abnormal formation or damages of myelin or OLs underlie myelin pathologies, which are characterized by severe neurological deficits. Accumulating evidence are showing anti-inflammatory and neuroprotective effects in several in vitro and in vivo models of neuroinflammation and neurodegeneration exerted by translocator protein (TSPO) ligands. In the present thesis, we attempted to investigate several aspects of myelin diseases in order to find innovative therapeutic approaches. Our first results showed that TSPO negatively modulates microglia activation towards the classical inflammatory phenotype. After, we demonstrated the beneficial effect of the administration of two TSPO ligands in a murine model of MS by the evaluation of pathological markers. Finally, we proved that TSPO may possess also an important role during OLs differentiation, thus proposing TSPO as a promising target to promote remyelination.