27Motor symptoms of Parkinson's disease (PD) are caused by degeneration and progressive loss 28 of nigrostriatal dopamine neurons. Currently no cure for this disease is available. Existing drugs 29 alleviate PD symptoms, but fail to halt neurodegeneration. Glial cell line-derived neurotrophic factor 30 (GDNF) is able to protect and repair dopamine neurons in vitro and in animal models of PD, but its 31 clinical use is complicated by pharmacokinetic properties. In the present study we demonstrate the 32 ability of a small molecule agonist of GDNF receptor RET to support the survival of cultured 33 dopamine neurons only when they express GDNF receptors. In addition, BT13 activates intracellular 34 signaling cascades in vivo, stimulates release of dopamine and protect the function of dopaminergic 35 neurons in a 6-hydroxydopamine (6-OHDA) rat model of PD. In contrast to GDNF, BT13 is able to 36 penetrate through the blood-brain-barrier. Thus, BT13 serves as an excellent tool compound for the 37 development of novel disease-modifying treatments against PD. 38 39

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