The Park6 from of idiopathic Parkinson`s disease: Characterization of patients, their cells, and functional role of Pink1 kinase

• Antragsteller: Professor Dr. Georg Auburger
• Fachliche Zuordnung: Molekulare Biologie und Physiologie von Nerven- und Gliazellen
• Förderung: Förderung von 2004 bis 2009
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5446392

Eleven genes (Park1-11) have been described in hereditary Parkinson`s disease (PD) variants since 1997. Insight into the mechanisms of pathology should come easiest from autosomal recessive forms like Park2/6/7, where loss of function mutations can initiate pathogenesis. Oxidative pathways have recently been found abnormal in Park2/6/7, and oxidative stress is well documented in late onset sporadic PD brains. After our recent collaborative identification of the serine threonine kinase Pink1 as the Park6 gene, we continue to study our Park6 family with 7 sibs (3 patients, 3 carriers), who have been compliant with skin and muscle biopsies. We plan to further investigate (I.) the affection of the nigrostriatal system versus other neuronal systems using clinical, electrophysiological, and imaging techniques, (II.) oxidative pathways in lymphoblasts, fibroblasts and muscle, (III.) mechanisms of activation of Pink1 kinase and Pink1-interacting proteins. This approach will help to better understand the molecular basis of Pink1 functions in the pathogenesis of PD and possibly define target molecules for novel therapies aimed to prevent neurodegeneration in Parkinson`s disease.

• DFG-Verfahren: Sachbeihilfen