Shh signaling involvement in demyelination- remyelination process

FRANCO P; ADAMO A; MATHIEU P; HALFON J; PAGANELLI A

Buenos Aires

Congreso; Reunion Conjunta de Sociedades Biomedicas; 2017

SAIC

Multiple sclerosis (MS) is one of the most common neurological disorders affecting young people worldwide. MS is characterized by inflammation, and demyelination; in turn, spontaneous remyelination is driven by oligodendroglial precursor cells (OPCs) but is usually incomplete, as OPCs fail to mature into myelinating oligodencrocytes (OLs), thus leading to neurodegeneration. Among several signaling pathways taking part in OPC maturation, Sonic hedgehog (Shh) has been recently shown to attenuate myelin damage through an increase in OPC number and maturation in a focal demyelination model. The transduction of hedgehog signaling classically involves transmembrane proteins Patched (Ptc) and Smoothened (Smo). In the absence of Shh ligand, downstream hedgehog signaling is repressed, as Ptc suppresses Smo and inhibits the Gli transcription factors to act on target genes. This repression is relieved when Shh binds Ptc. In this context, the aim of this work was to study Shh signaling during demyelination and remyelination of corpus callosum (CC) in a cuprizone (CPZ)-induced demyelination model in rats, and to further investigate Shh protein as a potential biomarker of different stages of MS.