Growth/differentiation Factor-15 (GDF-15), a Novel Member of the TGF-beta Superfamily, Promotes Survival of Lesioned Mesencephalic Dopaminergic Neurons in Vitro and in Vivo and is Induced in Neurons Following Cortical Lesioning.

This review summarizes the evidence that GDF-15, a recently discovered member of the TGF-beta superfamily, is a trophic factor for nigral dopamine neurons, both in vitro and in vivo. Specifically, GDF-15 promotes survival and differentiation of embryonic rat dopaminergic neurons, but not of other neuron populations, with the exception of serotonergic raphe neurons. The neurotrophic effect of GDF-15 seems to be direct and not mediated through glial cells. In the rat 6-hydroxydopamine model of parkinsonism GDF-15 rescues intoxicated dopaminergic neurons and abolishes abnormal turning behavior. The most prominent site of synthesis of GDF-15 within the brain is the choroid plexus, which secretes GDF-15 into the cerebrospinal fluid, from where the molecule can penetrate through the ependymal layer into the parenchyma. Analysis of mouse mutants lacking GDF-15 will reveal whether the endogenous factor also has a role in promoting embryonic and protecting lesioned nigral dopamine neurons.