Parkinson\'s disease is characterized by the progressive loss of the dopaminergic neurons in thesubstantia Ingra pars compact which results in functional changes in structures of the basal ganglia such as the sub thalamic nucleus, the entopeduncular nucleus and the substantial Ingra pars reticulata. Current therapies involve dopamine pharmacological treatment, deep brain stimulation and fatal cell transplantation. Though these approaches reach significant beneficial effects, they are however hampered by numerous limiting factors such as side effects or difficulties related to the methodology. Since a few years, significant progress has been made in the field of gene therapy for Parkinson\'disease, focusing on two main strategies: the replacement of biosynthetic enzymes for dopamine synthesis and the addition of neurotrophic factors for protection and restoration of dopaminergicneurons. Although successful vehicles have been developed and efficacy and safety have been shown in various animal models of Parkinson\'s disease, the cellular and molecular mechanisms underlying these benefits at different levels of the basal ganglia are so far incompletely known. This project will thus aim at characterizing these mechanisms particularly in the sub thalamic nucleus, entopeduncular nucleus and substance Ingra pars reticulate and evaluating the more efficient strategy which might be used inhuman therapy ursine combination of several strategies.'
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