TROPHIC AND PROTECTIVE EFFECTS OF GROWTH-DIFFERENTIATION FACTOR-5, A MEMBER OF THE TRANSFORMING GROWTH-FACTOR-BETA SUPERFAMILY, ON MIDBRAINDOPAMINERGIC-NEURONS

Growth/differentiation factor 5 (GDF5) is a novel member of the transf orming growth factor-beta (TGF-beta) superfamily of multifunctional cy tokines, We show here that GDF5 is expressed in the developing CNS inc luding the mesencephalon and acts as a neurotrophic, survival promotin g molecule for rat dopaminergic midbrain neurons, which degenerate in Parkinson's disease, Recombinant human GDF5 supports dopaminergic neur ons, dissected at embryonic day (E) 14 and cultured for 8 days under s erum-free conditions, to almost the same extent as TGF-beta 3, and is as effective as glial cell line-derived neurotrophic factor (GDNF), tw o established trophic factors for midbrain dopaminergic neurons, In co ntrast to TGF-beta and GDNF, GDF5 augments numbers of astroglial cells in the cultures, suggesting that it may act indirectly and through pa thways different from those triggered by TGF-beta and GDNF. GDF5 also protects dopaminergic neurons against the toxicity of N-methylpyridini um ion (MPP(+)), which selectively damages dopaminergic neurons throug h mechanisms currently debated in the etiology of Parkinson's disease (PD), GDF5 may therefore now be tested in animal models of PD and migh t become useful in the treatment of PD. (C) 1995 Wiley-Liss, Inc.