title: Neurotrophic effects of growth/differentiation factor 5 in a neuronal cell line.
abstract: The neurotrophin growth/differentiation factor 5 (GDF5) is studied as a potential therapeutic agent for Parkinson's 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 cultures 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 GDF5's 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.
authors.affiliation: Department of Anatomy and Neuroscience, University College Cork, College Road, Cork, Ireland. a.toulouse@ucc.ie
authors.forename: André
authors.initials: A
authors.lastname: Toulouse
authors.forename: Grace C
authors.initials: GC
authors.lastname: Collins
authors.forename: Aideen M
authors.initials: AM
authors.lastname: Sullivan
mesh_terms: D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics / Q000378:metabolism; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D059290:Dopaminergic Neurons / Q000166:cytology* / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D055428:Growth Differentiation Factor 5 / Q000494:pharmacology*; D006801:Humans; D009447:Neuroblastoma; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000188:drug therapy*; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013565:Sympatholytics / Q000633:toxicity; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
chemical_list: C525893:GDF5 protein, human; D055428:Growth Differentiation Factor 5; D013565:Sympatholytics; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; C078717:ROR2 protein, human; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; C498211:BMPR1A protein, human; C498214:BMPR1B protein, human; C498218:BMPR2 protein, human; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II