Neurotrophic factors NGF and FGF-2 alter levels of huntingtin (IT15) in striatal neuronal cell cultures

A mutation of the human IT15 gene is responsible for Huntington's disease ( HD) and the causative factor in the major neuronal loss observed in the str iatum. The growth factors basic fibroblast growth factor (FGF-2), nerve gro wth factor (NGF), and brain-derived neurotrophic factor (BDNF) improve surv ival and promote differentiation of striatal neurons, as well as exert a ne uroprotective effect when such neurons are challenged with metabolic toxins or excitatory amino acids. Using Western blotting and striatal cell cultur es, we found that FGF-2 increased the level of huntingtin in a dose-depende nt fashion, whereas NGF decreased huntingtin expression. The neurotrophic f actor-specific, dose-dependent effect on striatal levels of huntingtin may be relevant to understanding the normal role of IT15 and developing new the rapies against the disease provoking mutated IT15.