The bioenergetic status relates to dopamine neuron loss in familial PD with PINK1 mutations.

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 d...

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Autores principales:	Rüediger Hilker, Ulrich Pilatus, Carsten Eggers, Johann Hagenah, Julia Roggendorf, Simon Baudrexel, Johannes C Klein, Bernd Neumaier, Gereon R Fink, Helmuth Steinmetz, Christine Klein, Elke Hattingen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2a51e3e1ab3346638b11aeb6aeb35cb0
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spelling	oai:doaj.org-article:2a51e3e1ab3346638b11aeb6aeb35cb02021-11-18T08:05:45ZThe bioenergetic status relates to dopamine neuron loss in familial PD with PINK1 mutations.1932-620310.1371/journal.pone.0051308https://doaj.org/article/2a51e3e1ab3346638b11aeb6aeb35cb02012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23251494/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Mutations 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 ((31)P) and proton ((1)H) 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 K(i) 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.Rüediger HilkerUlrich PilatusCarsten EggersJohann HagenahJulia RoggendorfSimon BaudrexelJohannes C KleinBernd NeumaierGereon R FinkHelmuth SteinmetzChristine KleinElke HattingenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e51308 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rüediger Hilker Ulrich Pilatus Carsten Eggers Johann Hagenah Julia Roggendorf Simon Baudrexel Johannes C Klein Bernd Neumaier Gereon R Fink Helmuth Steinmetz Christine Klein Elke Hattingen The bioenergetic status relates to dopamine neuron loss in familial PD with PINK1 mutations.
description	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 ((31)P) and proton ((1)H) 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 K(i) 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.
format	article
author	Rüediger Hilker Ulrich Pilatus Carsten Eggers Johann Hagenah Julia Roggendorf Simon Baudrexel Johannes C Klein Bernd Neumaier Gereon R Fink Helmuth Steinmetz Christine Klein Elke Hattingen
author_facet	Rüediger Hilker Ulrich Pilatus Carsten Eggers Johann Hagenah Julia Roggendorf Simon Baudrexel Johannes C Klein Bernd Neumaier Gereon R Fink Helmuth Steinmetz Christine Klein Elke Hattingen
author_sort	Rüediger Hilker
title	The bioenergetic status relates to dopamine neuron loss in familial PD with PINK1 mutations.
title_short	The bioenergetic status relates to dopamine neuron loss in familial PD with PINK1 mutations.
title_full	The bioenergetic status relates to dopamine neuron loss in familial PD with PINK1 mutations.
title_fullStr	The bioenergetic status relates to dopamine neuron loss in familial PD with PINK1 mutations.
title_full_unstemmed	The bioenergetic status relates to dopamine neuron loss in familial PD with PINK1 mutations.
title_sort	bioenergetic status relates to dopamine neuron loss in familial pd with pink1 mutations.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/2a51e3e1ab3346638b11aeb6aeb35cb0
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The bioenergetic status relates to dopamine neuron loss in familial PD with PINK1 mutations.

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