Molecular mechanisms of GCH1-associated Parkinson's disease.
GCH1 mutations are a known cause of dopamine-responsive dystonia. GCH1 mutations lead to reduced levels of tetrahydrobiopterin (BH4), an important cofactor in the dopamine synthesis pathway. BH4 also exhibits anti-oxidative properties. Very recently, a new link was discovered between GCH1 mutations and the risk of Parkinson´s disease. My research project focuses on unraveling the mechanisms by which GCH1 mutations predispose to nigrostriatal cell death. This will be investigated by experiments in fibroblasts from patients with GCH1 mutations, iPSC-derived dopaminergic neurons from these patients and Drosophila models.