TGFbeta1 in Huntington Disease: a new disease mechanism and potential biomarker

Huntington Disease (HD) is a neurodegenerative disorder caused by a CAG expanded mutation in HTT gene encoding for huntingtin protein (htt). The resulting mutant hungtintin (mhtt) interferes with essential biological processes such as neurotrophins production and release. Recently, we have reported an early defect in TGFbeta1 production in different models of HD. TGFbeta1 is a pleiotropic cytokine with an established neuroprotective function and a powerful anti-inflammatory role. In the central nervous system TGFbeta1 is predominantly expressed in glial cells and peripherically is mainly produced by macrophages, myeloid-derived immune cells. Based on these considerations, we will investigate whether the perturbation of TGFbeta1 levels in HD macrophages reflects central defects over the time. By our project therefore, we aim to find new possible link between central and peripheral dysfunction in attempt to identify a novel possible disease progression related marker.