**7. Relevance of 6-OHDA model in gene therapy**

The 6-OHDA injury model has been used to demonstrate the benefits of neurotrophic therapy (NT) [102]. NT consists of directed delivery of genes encoding neurotrophic factors such as brain derived neurotrophic factor (BDNF) [103], glial cell line-derived neurotrophic factor (GDNF) [104–109], cerebral dopamine neurotrophic factor (CDNF) [76, 110], mesencephalic astrocyte-derived neurotrophic factor (MANF) [111], vascular endothelial growth factor (VEGF) [112] through nanoparticles [113, 114], or through viral or non-viral gene vectors [76, 104–107, 115]. The purpose of NT assessed in the 6-OHDA model is to prevent the progression of neurodegeneration and to stimulate the functional regeneration of the nigrostriatal system [116, 117]. The recovery of dopaminergic populations could improve motor function. It is therefore important to identify further underlying mechanisms of oxidative stress, neuroinflammation, neurodegeneration and neuronal death caused by 6-OHDA. This knowledge is the key to discovery novel therapies to treat PD.
