TY  - JOUR
A1  - Hilker, Rüdiger
A1  - Pilatus, Ulrich
A1  - Eggers, Carsten
A1  - Hagenah, Johann Meinert
A1  - Roggendorf, Julia
A1  - Baudrexel, Simon
A1  - Klein, Johannes Christian
A1  - Neumaier, Bernd
A1  - Fink, Gereon Rudolf
A1  - Steinmetz, Helmuth
A1  - Klein, Christine
A1  - Hattingen, Elke
T1  - The bioenergetic status relates to dopamine neuron loss in familial PD with PINK1 mutations
T2  - PLoS One
N2  - Mutations in the PINK1 gene cause autosomal recessive familial Parkinson’s disease (PD). The gene encodes a mitochondrial protein kinase that plays an important role in maintaining mitochondrial function and integrity. However, the pathophysiological link between mutation-related bioenergetic deficits and the degenerative process in dopaminergic neurons remains to be elucidated. We performed phosphorous (31P) and proton (1H) 3-T magnetic resonance spectroscopic imaging (MRSI) in 11 members of a German family with hereditary PD due to PINK1 mutations (PARK6) compared to 23 age-matched controls. All family members had prior 18-Fluorodopa (FDOPA) positron emission tomography (PET). The striatal FDOPA uptake was correlated with quantified metabolic brain mapping in MRSI. At group level, the heterozygous PINK1 mutation carriers did not show any MRSI abnormalities relative to controls. In contrast, homozygous individuals with manifest PD had putaminal GPC, PCr, HEP and β-ATP levels well above the 2SD range of controls. Across all subjects, the FDOPA Ki values correlated positively with MI (r = 0.879, p<0.001) and inversely with β-ATP (r = −0.784, p = 0.008) and GPC concentrations (r = −0.651, p = 0.030) in the putamen. Our combined imaging data suggest that the dopaminergic deficit in this family with PD due to PINK1 mutations relates to osmolyte dysregulation, while the delivery of high energy phosphates was preserved. Our results corroborate the hypothesis that PINK1 mutations result in reduced neuronal survival, most likely due to impaired cellular stress resistance.
Y1  - 2012
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/27523
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-275235
SN  - 1932-6203
N1  - Licensed under a Creative Commons Attribution License. http://creativecommons.org/licenses/by/2.5/
VL  - 7
IS  - 12: e51308
PB  - PLoS
CY  - Lawrence, Kan.
ER  -