Modifiers of PINK1 function in Parkinson's disease

• Applicant: Dr. Norman Kock
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: from 2006 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 27685545

• Final Report Year: 2009

Final Report Abstract

Parkinson’s disease (PD) is associated with loss of dopaminergic cells and genetically linked to proteins that function in the management of cellular stress resulting from protein misfolding and oxidative damage. Mutations in the recently discovered PINK1 gene cause autosomal recessive PD. The main objective of this research study was to determine the molecular pathway of PINK1 and impact of mutated forms. We performed a mass spectroscopy analysis, using Stratagene’s Interplay Tandem Affinity Purification (TAP) system to identify novel interactors of PINK1. Several potential interactors have been identified, however confirmation studies are pending. Further, we could demonstrate that human skin fibroblasts containing mutated PINK1 display a mitochondrial dysfunction, with a p.V170G PINK1 mutation having an effect particularly on the respiratory chain.

Publications

• Differential effects of PINK1 nonsense and missense mutations on mitochondrial function and morphology. AAN 2009. Supplement to Neurology Volume 72, Number 11, Supplement 3, Abstract P08.090
  Grünewald A, Gegg ME, Taanman JW, King RH, Klein C, Schapira AHV