Parkinson’s disease (PD) is characterised by midbrain dopaminergic neuron degeneration resulting from intraneuronal a-synuclein (aSyn) accumulation. Adeno-associated virus (AAV)-mediated delivery of neurotrophic factors (NTFs), including GDNF, has been tested in clinical trials and has potential to be used as disease-modifying therapy for PD. We have previously shown that the NTF growth/differentiation factor 5 (GDF5) exerts neuroprotective effects after intranigral delivery in an aSyn rat model of PD. Here we examined whether delivery of GDF5 and GDNF to the striatum (putamen), a more clinically-accessible site than the nigra, also exerted neuroprotective effects in the aSyn rat PD model. Following baseline behavioural testing, female Sprague-Dawley rats (n=24) received unilateral intranigral injection of AAV-aSyn and unilateral instrastriatal injection of either AAV-Null, AAV-GDF5, or AAV-GDNF. Behavioural testing was carried out after 12, 16 and 20 weeks. After 24 weeks, brains were stained for tyrosine hydroxylase (TH) and inflammatory markers. Strong ipsilateral GDNF and GDF5 overexpression was observed in the nigra, showing that GDNF and GDF5 had been retrogradely transported to the nigra from the striatal injection site. However, there were no significant differences between numbers of dopaminergic neurons in the ipsilateral nigra, or striatal dopaminergic terminals, between the groups. No significant differences were observed between groups in the cylinder or the grid-walking tests. These data indicate that striatal delivery of GDNF or GDF5 did not have significant protective effects on the nigrostriatal dopaminergic neurons against aSyn-induced degeneration, which provides important information on the optimal injection site for future trials.