Projects in the lab

One major focus of the group is the elucidation of molecular signaling pathways leading to neurodegeneration in Parkinson's disease. Using mutation screenings in a large sample of German PD patients, we identified novel mutations in genes that are responsible for familial PD and deciphered genetic variants in candidate genes that are associated with sporadic PD. We intensively study functional consequences of the identified mutations, investigating molecular signalling cascades in the pathogenesis of PD. In this context, we are interested in the identification of novel interacting proteins, characterization of proteasomal function, analysis of mitochondrial homeostasis, and the effects of cell viability in cellular models of the disease. These studies focus on the development of novel neuroprotective therapeutic strategies in the treatment of PD as the most common neurodegenerative movement disorder.

Key publications

Burbulla LF, Schelling C, Kato H, Rapaport D, Woitalla D, Schiesling C, Schulte C, Sharma M, Bauer P, Jung S, Nordheim A, Schöls L, Riess O, Krüger R. (2010) Dissecting the Role of the Mitochondrial Chaperone Mortalin in Parkinson’s Disease – Functional Impact of Disease-Related Variants on Mitochondrial Homeostasis. Hum Mol Genet (published online 16.09.2010; doi:10.1093/hmg/ddq370)

Krebiehl G, Ruckerbauer S, Burbulla L, Kieper N, Maurer B, Waak J, Wolburg H, Gizatullina Z, Gellerich F, Woitalla D, Riess O, Kahle PJ, Proikas-Cezanne T, Krüger R. (2010) Reduced basal autophagy and impaired mitochondrial dynamics due to loss of Parkinson’s disease-associated protein DJ-1. PLoS One 5: e9367

Kieper N, Holmström K, Ciceri D, Fiesel F, Wolburg H, Ziviani E, Whitworth A, Martins LM, Kahle PJ, Krüger R. (2010) Modulation of mitochondrial function and morphology by interaction of Omi/HtrA2 with the mitochondrial fusion factor OPA1. Exp Cell Res 316: 1213-1224

Seidel K, Schöls L, Nuber S, Petrasch-Parwez E, Gierga K, Wszolek Z, Dickson D, Gai WP, Bornemann A, Riess O, Rami A, den Dunnen WFA, Deller T, Rüb U, Krüger R. (2010) First appraisal of brain pathology owing to A30P mutant alpha-synuclein. Ann Neurol 67: 684-689

Strauss KM, Martins LM,  Plun-Favreau H, Marx FP, Kautzmann S, Berg D, Gasser T, Wszolek Z, Müller T, Bornemann A, Wolburg H, Downward J, Riess O, Schulz JB, Krüger R. (2005) Loss of function mutation in the gene encoding Omi/HtrA2 in Parkinson's disease. Hum Mol Genet 14: 2099-2111

Patents

German Patent No.: 10200 400 4924‚ A141S und G399S mutations in the Omi/HtrA2 protein in Parkinson's disease

US Patent and European Patent pending.