The neurotrophin growth/differentiation factor 5 (GDF5) is studied as a
potential therapeutic agent for Parkinsonís disease
as it is believed to play a role in the development and
maintenance of the nigrostriatal system. Progress in understanding
the effects of GDF5 on dopaminergic neurones has been
hindered by the use of mixed cell populations derived from primary
or in vivo experiments, making it difficult to differentiate
between direct and indirect effects of GDF5 treatment on neurones.
In an attempt to establish an useful model to study the
direct neuronal influence of GDF5, we have characterised the effects
of GDF5 on a human neuronal cell line, SH-SY5Y. Our results
show that GDF5 has the capability to promote neuronal but not
dopaminergic differentiation. We also show that it promotes
neuronal survival in vitro following a 6-hydroxydopamine insult.
Our results show that application of GDF5 to SH-SY5Y
cultures induces the SMAD pathway which could potentially be implicated
in the intracellular transmission of GDF5ís neurotrophic
effects. Overall, our study shows that the SH-SY5Y neuroblastoma
cell line provides an excellent neuronal model to study the
neurotrophic effects of GDF5.