STRAP and NME1 Mediate the Neurite Growth-Promoting Effects of the Neurotrophic Factor GDF5

The loss of midbrain dopaminergic (mDA) neurons and their axons is central to Parkinson’s disease (PD). Growth differentiation factor (GDF)5 has been proposed as a neurotrophic factor for PD therapy. However the molecular mediators of its neurotrophic action are unknown. To address this, we performed proteomics analysis and identified that GDF5 increases the expression of two proteins, serine threonine receptor associated protein kinase (STRAP) and nucleoside diphosphate kinase (NME)1, in the SH-SY5Y neuronal cell line. We show that mRNAs encoding these proteins are expressed in the developing and adult midbrain in vivo. We also report that the expression of both STRAP and NME1 is necessary and sufficient for the promotion of neurite growth by GDF5 on SH-SY5Y cells. In summary, we identify NME1 and STRAP as key mediators of the neurotrophic effects of GDF5, which rationalises their further study as therapeutic targets for the protection of dopaminergic neurons in PD.

Suggested Citation: Suggested Citation

Anantha, Jayanth and Wyatt, Sean and Sullivan, Aideen and O'Keeffe, Gerard, STRAP and NME1 Mediate the Neurite Growth-Promoting Effects of the Neurotrophic Factor GDF5. Available at SSRN: https://ssrn.com/abstract=3571299 or http://dx.doi.org/10.2139/ssrn.3571299

This version of the paper has not been formally peer reviewed.