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Project

Pathogenic mechanisms of GCH1-associated Parkinson's disease

Parkinson’s disease is a common brain disease characterized by slowness of movement, tremor, falls, dementia and many other problems. There is still no therapy that slows down its relentless progression. In Parkinson’s disease dopamine-producing nerve cells in the brain gradually become sick and eventually die. Why these cells die, is not well understood. In rare familial cases Parkinson’s disease is caused by genetic mutations. Recently, it was discovered that mutations in the GCH1 gene strongly increase the risk of developing Parkinson’s disease. GCH1 codes for the enzyme GTP cyclohydrolase 1, which is required for the synthesis of tetrahydrobiopterin. Tetrahydrobiopterin is necessary for the production of dopamine, but also protects cells against damaging oxygen radicals. Parkinson’s disease-associated GCH1 mutations impair the ability to synthesize tetrahydrobiopterin, but how this leads to Parkinson’s disease is currently unknown. In this project we will investigate the mechanisms by which GCH1 mutations induce death of dopaminergic neurons. We will analyze the role of GCH1 and tetrahydrobiopterin in cellular health and survival in skin cells from patients with GCH1 mutations and healthy controls, in dopaminergic neurons derived from these skin cells and in dopaminergic neurons in the brains of fruit flies. Understanding the molecular link between GCH1 mutations and Parkinson’s disease will hopefully contribute to the development of better therapies.

Date:1 Jan 2017 →  31 Dec 2020
Keywords:GCH1, Pathogenic mechanisms, Parkinson's disease
Disciplines:Neurosciences, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing