3-hydroxykynurenine and other Parkinson's disease biomarkers discovered by metabolomic analysis.
Identifieur interne : 000B44 ( Main/Exploration ); précédent : 000B43; suivant : 000B453-hydroxykynurenine and other Parkinson's disease biomarkers discovered by metabolomic analysis.
Auteurs : Peter A. Lewitt [États-Unis] ; Jia Li ; Mei Lu ; Thomas G. Beach ; Charles H. Adler ; Lining GuoSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2013.
English descriptors
- KwdEn :
- Adult, Aged, Aged, 80 and over, Biological Markers (cerebrospinal fluid), Female, Glutathione (cerebrospinal fluid), Humans, Kynurenine (analogs & derivatives), Kynurenine (cerebrospinal fluid), Male, Mass Spectrometry, Metabolomics, Middle Aged, Oxidative Stress (physiology), Parkinson Disease (cerebrospinal fluid), Sensitivity and Specificity.
- MESH :
- chemical , analogs & derivatives : Kynurenine.
- chemical , cerebrospinal fluid : Biological Markers, Glutathione, Kynurenine.
- cerebrospinal fluid : Parkinson Disease.
- physiology : Oxidative Stress.
- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Mass Spectrometry, Metabolomics, Middle Aged, Sensitivity and Specificity.
Abstract
Parkinson's disease (PD) biomarkers are needed to enhance therapeutics research and to understand PD pathogenesis. Methods that simultaneously measure hundreds of small molecular-weight compounds-metabolomic analysis-"fingerprint" disease-specific alterations in individual compounds or metabolic pathways. Beyond a nontargeted search for PD biomarkers, we hypothesized that PD cerebrospinal fluid would show increased formation of the excitotoxin 3-hydroxykynurenine and diminished concentration of the antioxidant glutathione. Cerebrospinal fluid was collected at <4 hours postmortem from 48 pathologically-verified PD subjects and 57 comparably-aged controls. Assays involved ultra-high-performance liquid and gas chromatography linked to mass spectrometry. We used univariate techniques to determine fold-changes in concentrations of biochemicals; false-discovery rates were calculated to exclude spurious findings. Data was modeled using a Support Vector Machine for analyzing compounds selected by Welch's t test. Classification accuracy was determined by cross-validation. Of 243 structurally-identified biochemicals,19 compounds differentiated PD from controls at a 20% false-discovery level. In PD, mean 3-hydroxykynurenine concentration was increased by one-third, and mean oxidized glutathione was decreased by 40% (for each, P < .01). Four of the 19 compounds differentiating PD from controls were N-acetylated amino acids, suggesting a generalized alteration in N-acetylation activity. The Support Vector Machine classification model distinguished between groups at 83% sensitivity and 91% specificity for the learning data, and at 65% and 79% from cross-validation. In this study, the first for metabolomic profiling of PD cerebrospinal fluid, we found several novel biomarkers and offer new directions for recognizing disease-specific biochemical indicators. The findings support involvement of excitotoxicity and oxidative stress in the pathogenesis of PD.
DOI: 10.1002/mds.25555
PubMed: 23873789
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000818
- to stream PubMed, to step Curation: 000818
- to stream PubMed, to step Checkpoint: 000B52
- to stream Ncbi, to step Merge: 003C64
- to stream Ncbi, to step Curation: 003C64
- to stream Ncbi, to step Checkpoint: 003C64
- to stream Main, to step Merge: 000B44
- to stream Main, to step Curation: 000B44
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">3-hydroxykynurenine and other Parkinson's disease biomarkers discovered by metabolomic analysis.</title>
<author><name sortKey="Lewitt, Peter A" sort="Lewitt, Peter A" uniqKey="Lewitt P" first="Peter A" last="Lewitt">Peter A. Lewitt</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Neurology, Henry Ford Hospital, West Bloomfield, Michigan, USA; School of Medicine, Wayne State University, Detroit, Michigan, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Henry Ford Hospital, West Bloomfield, Michigan, USA; School of Medicine, Wayne State University, Detroit, Michigan</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Li, Jia" sort="Li, Jia" uniqKey="Li J" first="Jia" last="Li">Jia Li</name>
</author>
<author><name sortKey="Lu, Mei" sort="Lu, Mei" uniqKey="Lu M" first="Mei" last="Lu">Mei Lu</name>
</author>
<author><name sortKey="Beach, Thomas G" sort="Beach, Thomas G" uniqKey="Beach T" first="Thomas G" last="Beach">Thomas G. Beach</name>
</author>
<author><name sortKey="Adler, Charles H" sort="Adler, Charles H" uniqKey="Adler C" first="Charles H" last="Adler">Charles H. Adler</name>
</author>
<author><name sortKey="Guo, Lining" sort="Guo, Lining" uniqKey="Guo L" first="Lining" last="Guo">Lining Guo</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2013">2013</date>
<idno type="RBID">pubmed:23873789</idno>
<idno type="pmid">23873789</idno>
<idno type="doi">10.1002/mds.25555</idno>
<idno type="wicri:Area/PubMed/Corpus">000818</idno>
<idno type="wicri:Area/PubMed/Curation">000818</idno>
<idno type="wicri:Area/PubMed/Checkpoint">000B52</idno>
<idno type="wicri:Area/Ncbi/Merge">003C64</idno>
<idno type="wicri:Area/Ncbi/Curation">003C64</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">003C64</idno>
<idno type="wicri:Area/Main/Merge">000B44</idno>
<idno type="wicri:Area/Main/Curation">000B44</idno>
<idno type="wicri:Area/Main/Exploration">000B44</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">3-hydroxykynurenine and other Parkinson's disease biomarkers discovered by metabolomic analysis.</title>
<author><name sortKey="Lewitt, Peter A" sort="Lewitt, Peter A" uniqKey="Lewitt P" first="Peter A" last="Lewitt">Peter A. Lewitt</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Neurology, Henry Ford Hospital, West Bloomfield, Michigan, USA; School of Medicine, Wayne State University, Detroit, Michigan, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Henry Ford Hospital, West Bloomfield, Michigan, USA; School of Medicine, Wayne State University, Detroit, Michigan</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Li, Jia" sort="Li, Jia" uniqKey="Li J" first="Jia" last="Li">Jia Li</name>
</author>
<author><name sortKey="Lu, Mei" sort="Lu, Mei" uniqKey="Lu M" first="Mei" last="Lu">Mei Lu</name>
</author>
<author><name sortKey="Beach, Thomas G" sort="Beach, Thomas G" uniqKey="Beach T" first="Thomas G" last="Beach">Thomas G. Beach</name>
</author>
<author><name sortKey="Adler, Charles H" sort="Adler, Charles H" uniqKey="Adler C" first="Charles H" last="Adler">Charles H. Adler</name>
</author>
<author><name sortKey="Guo, Lining" sort="Guo, Lining" uniqKey="Guo L" first="Lining" last="Guo">Lining Guo</name>
</author>
</analytic>
<series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title>
<idno type="eISSN">1531-8257</idno>
<imprint><date when="2013" type="published">2013</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Biological Markers (cerebrospinal fluid)</term>
<term>Female</term>
<term>Glutathione (cerebrospinal fluid)</term>
<term>Humans</term>
<term>Kynurenine (analogs & derivatives)</term>
<term>Kynurenine (cerebrospinal fluid)</term>
<term>Male</term>
<term>Mass Spectrometry</term>
<term>Metabolomics</term>
<term>Middle Aged</term>
<term>Oxidative Stress (physiology)</term>
<term>Parkinson Disease (cerebrospinal fluid)</term>
<term>Sensitivity and Specificity</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Kynurenine</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="cerebrospinal fluid" xml:lang="en"><term>Biological Markers</term>
<term>Glutathione</term>
<term>Kynurenine</term>
</keywords>
<keywords scheme="MESH" qualifier="cerebrospinal fluid" xml:lang="en"><term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Oxidative Stress</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Female</term>
<term>Humans</term>
<term>Male</term>
<term>Mass Spectrometry</term>
<term>Metabolomics</term>
<term>Middle Aged</term>
<term>Sensitivity and Specificity</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Parkinson's disease (PD) biomarkers are needed to enhance therapeutics research and to understand PD pathogenesis. Methods that simultaneously measure hundreds of small molecular-weight compounds-metabolomic analysis-"fingerprint" disease-specific alterations in individual compounds or metabolic pathways. Beyond a nontargeted search for PD biomarkers, we hypothesized that PD cerebrospinal fluid would show increased formation of the excitotoxin 3-hydroxykynurenine and diminished concentration of the antioxidant glutathione. Cerebrospinal fluid was collected at <4 hours postmortem from 48 pathologically-verified PD subjects and 57 comparably-aged controls. Assays involved ultra-high-performance liquid and gas chromatography linked to mass spectrometry. We used univariate techniques to determine fold-changes in concentrations of biochemicals; false-discovery rates were calculated to exclude spurious findings. Data was modeled using a Support Vector Machine for analyzing compounds selected by Welch's t test. Classification accuracy was determined by cross-validation. Of 243 structurally-identified biochemicals,19 compounds differentiated PD from controls at a 20% false-discovery level. In PD, mean 3-hydroxykynurenine concentration was increased by one-third, and mean oxidized glutathione was decreased by 40% (for each, P < .01). Four of the 19 compounds differentiating PD from controls were N-acetylated amino acids, suggesting a generalized alteration in N-acetylation activity. The Support Vector Machine classification model distinguished between groups at 83% sensitivity and 91% specificity for the learning data, and at 65% and 79% from cross-validation. In this study, the first for metabolomic profiling of PD cerebrospinal fluid, we found several novel biomarkers and offer new directions for recognizing disease-specific biochemical indicators. The findings support involvement of excitotoxicity and oxidative stress in the pathogenesis of PD.</div>
</front>
</TEI>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Michigan</li>
</region>
</list>
<tree><noCountry><name sortKey="Adler, Charles H" sort="Adler, Charles H" uniqKey="Adler C" first="Charles H" last="Adler">Charles H. Adler</name>
<name sortKey="Beach, Thomas G" sort="Beach, Thomas G" uniqKey="Beach T" first="Thomas G" last="Beach">Thomas G. Beach</name>
<name sortKey="Guo, Lining" sort="Guo, Lining" uniqKey="Guo L" first="Lining" last="Guo">Lining Guo</name>
<name sortKey="Li, Jia" sort="Li, Jia" uniqKey="Li J" first="Jia" last="Li">Jia Li</name>
<name sortKey="Lu, Mei" sort="Lu, Mei" uniqKey="Lu M" first="Mei" last="Lu">Mei Lu</name>
</noCountry>
<country name="États-Unis"><region name="Michigan"><name sortKey="Lewitt, Peter A" sort="Lewitt, Peter A" uniqKey="Lewitt P" first="Peter A" last="Lewitt">Peter A. Lewitt</name>
</region>
</country>
</tree>
</affiliations>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Santé/explor/MovDisordV3/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000B44 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000B44 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Santé |area= MovDisordV3 |flux= Main |étape= Exploration |type= RBID |clé= pubmed:23873789 |texte= 3-hydroxykynurenine and other Parkinson's disease biomarkers discovered by metabolomic analysis. }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:23873789" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \ | NlmPubMed2Wicri -a MovDisordV3
This area was generated with Dilib version V0.6.23. |