ParkinsonCanadaV1, Main, Exploration, bibRecord, 002980

Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress

Identifieur interne : 002980 ( Main/Exploration ); précédent : 002979; suivant : 002981

Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress

Auteurs : Raymond H. Kim [Canada] ; Patrice D. Smith [Canada] ; Hossein Aleyasin [Canada] ; Shawn Hayley [Canada] ; Matthew P. Mount [Canada] ; Scott Pownall [Canada] ; Andrew Wakeham [Canada] ; Annick J. You-Ten [Canada] ; Suneil K. Kalia [Canada] ; Patrick Horne [Canada] ; David Westaway [Canada] ; Andres M. Lozano [Canada] ; Hymie Anisman [Canada] ; David S. Park [Canada] ; Tak W. Mak [Canada]

Source :

Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2005.

RBID : PMC:555037

English descriptors

KwdEn :
- Animals, Base Sequence, Cell Death, Corpus Striatum (drug effects), Corpus Striatum (metabolism), Corpus Striatum (pathology), DNA, Complementary (genetics), Denervation, Gene Targeting, Humans, Intracellular Signaling Peptides and Proteins, MPTP Poisoning (metabolism), Mice, Mice, Inbred C57BL, Mice, Knockout, Motor Activity, Neurons (cytology), Neurons (metabolism), Oncogene Proteins (deficiency), Oncogene Proteins (genetics), Oncogene Proteins (metabolism), Oxidative Stress, Parkinson Disease (genetics), Parkinson Disease (metabolism), Parkinsonian Disorders (genetics), Parkinsonian Disorders (metabolism), Parkinsonian Disorders (physiopathology), Protein Deglycase DJ-1.
MESH :
- chemical , deficiency : Oncogene Proteins.
- chemical , genetics : DNA, Complementary, Oncogene Proteins.
- cytology : Neurons.
- drug effects : Corpus Striatum.
- genetics : Parkinson Disease, Parkinsonian Disorders.
- metabolism : Corpus Striatum, MPTP Poisoning, Neurons, Oncogene Proteins, Parkinson Disease, Parkinsonian Disorders.
- pathology : Corpus Striatum.
- physiopathology : Parkinsonian Disorders.
- Animals, Base Sequence, Cell Death, Denervation, Gene Targeting, Humans, Intracellular Signaling Peptides and Proteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Motor Activity, Oxidative Stress, Protein Deglycase DJ-1.

Abstract

Mutations of the DJ-1 (PARK7) gene are linked to familial Parkinson's disease. We used gene targeting to generate DJ-1-deficient mice that were viable, fertile, and showed no gross anatomical or neuronal abnormalities. Dopaminergic neuron numbers in the substantia nigra and fiber densities and dopamine levels in the striatum were normal. However, DJ-1–/– mice showed hypolocomotion when subjected to amphetamine challenge and increased striatal denervation and dopaminergic neuron loss induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine. DJ-1–/–embryonic cortical neurons showed increased sensitivity to oxidative, but not nonoxidative, insults. Restoration of DJ-1 expression to DJ-1–/– mice or cells via adenoviral vector delivery mitigated all phenotypes. WT mice that received adenoviral delivery of DJ-1 resisted 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine-induced striatal damage, and neurons overexpressing DJ-1 were protected from oxidative stress in vitro. Thus, DJ-1 protects against neuronal oxidative stress, and loss of DJ-1 may lead to Parkinson's disease by conferring hypersensitivity to dopaminergic insults.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC555037

DOI: 10.1073/pnas.0501282102
PubMed: 15784737
PubMed Central: 555037

Affiliations:

Le document en format XML

<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress</title>
<author><name sortKey="Kim, Raymond H" sort="Kim, Raymond H" uniqKey="Kim R" first="Raymond H." last="Kim">Raymond H. Kim</name>
<affiliation wicri:level="4"><nlm:aff id="N0x98a91e0.0x9eb80d0">Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada M5G 2C1;</nlm:aff>
<country>Canada</country>
<wicri:regionArea>Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Smith, Patrice D" sort="Smith, Patrice D" uniqKey="Smith P" first="Patrice D." last="Smith">Patrice D. Smith</name>
<affiliation wicri:level="1"><nlm:aff id="N0x98a91e0.0x9eb80d0">Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON, Canada K1H 8M5;</nlm:aff>
<country>Canada</country>
<wicri:regionArea>Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON</wicri:regionArea>
<wicri:noRegion>ON</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Aleyasin, Hossein" sort="Aleyasin, Hossein" uniqKey="Aleyasin H" first="Hossein" last="Aleyasin">Hossein Aleyasin</name>
<affiliation wicri:level="1"><nlm:aff id="N0x98a91e0.0x9eb80d0">Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON, Canada K1H 8M5;</nlm:aff>
<country>Canada</country>
<wicri:regionArea>Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON</wicri:regionArea>
<wicri:noRegion>ON</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hayley, Shawn" sort="Hayley, Shawn" uniqKey="Hayley S" first="Shawn" last="Hayley">Shawn Hayley</name>
<affiliation wicri:level="1"><nlm:aff id="N0x98a91e0.0x9eb80d0">Institute for Neuroscience, Carleton University, Ottawa, ON, Canada K1H 6N5;</nlm:aff>
<country>Canada</country>
<wicri:regionArea>Institute for Neuroscience, Carleton University, Ottawa, ON</wicri:regionArea>
<wicri:noRegion>ON</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Mount, Matthew P" sort="Mount, Matthew P" uniqKey="Mount M" first="Matthew P." last="Mount">Matthew P. Mount</name>
<affiliation wicri:level="1"><nlm:aff id="N0x98a91e0.0x9eb80d0">Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON, Canada K1H 8M5;</nlm:aff>
<country>Canada</country>
<wicri:regionArea>Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON</wicri:regionArea>
<wicri:noRegion>ON</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Pownall, Scott" sort="Pownall, Scott" uniqKey="Pownall S" first="Scott" last="Pownall">Scott Pownall</name>
<affiliation wicri:level="1"><nlm:aff id="N0x98a91e0.0x9eb80d0">enGene Incorporated, Vancouver, BC, Canada V6T 1Z3;</nlm:aff>
<country>Canada</country>
<wicri:regionArea>enGene Incorporated, Vancouver, BC</wicri:regionArea>
<wicri:noRegion>BC</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wakeham, Andrew" sort="Wakeham, Andrew" uniqKey="Wakeham A" first="Andrew" last="Wakeham">Andrew Wakeham</name>
<affiliation wicri:level="4"><nlm:aff id="N0x98a91e0.0x9eb80d0">Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada M5G 2C1;</nlm:aff>
<country>Canada</country>
<wicri:regionArea>Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="You Ten, Annick J" sort="You Ten, Annick J" uniqKey="You Ten A" first="Annick J." last="You-Ten">Annick J. You-Ten</name>
<affiliation wicri:level="4"><nlm:aff id="N0x98a91e0.0x9eb80d0">Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada M5G 2C1;</nlm:aff>
<country>Canada</country>
<wicri:regionArea>Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kalia, Suneil K" sort="Kalia, Suneil K" uniqKey="Kalia S" first="Suneil K." last="Kalia">Suneil K. Kalia</name>
<affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="N0x98a91e0.0x9eb80d0">Division of Applied and Interventional Research, Toronto Western Hospital Research Institute, Toronto, ON, Canada M5T 2S8</nlm:aff>
<country>Canada</country>
<wicri:regionArea>Division of Applied and Interventional Research, Toronto Western Hospital Research Institute, Toronto, ON</wicri:regionArea>
<wicri:noRegion>ON</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Horne, Patrick" sort="Horne, Patrick" uniqKey="Horne P" first="Patrick" last="Horne">Patrick Horne</name>
<affiliation wicri:level="4"><nlm:aff id="N0x98a91e0.0x9eb80d0">Center for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada M5S 3H2</nlm:aff>
<country>Canada</country>
<wicri:regionArea>Center for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Westaway, David" sort="Westaway, David" uniqKey="Westaway D" first="David" last="Westaway">David Westaway</name>
<affiliation wicri:level="4"><nlm:aff id="N0x98a91e0.0x9eb80d0">Center for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada M5S 3H2</nlm:aff>
<country>Canada</country>
<wicri:regionArea>Center for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lozano, Andres M" sort="Lozano, Andres M" uniqKey="Lozano A" first="Andres M." last="Lozano">Andres M. Lozano</name>
<affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="N0x98a91e0.0x9eb80d0">Division of Applied and Interventional Research, Toronto Western Hospital Research Institute, Toronto, ON, Canada M5T 2S8</nlm:aff>
<country>Canada</country>
<wicri:regionArea>Division of Applied and Interventional Research, Toronto Western Hospital Research Institute, Toronto, ON</wicri:regionArea>
<wicri:noRegion>ON</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Anisman, Hymie" sort="Anisman, Hymie" uniqKey="Anisman H" first="Hymie" last="Anisman">Hymie Anisman</name>
<affiliation wicri:level="1"><nlm:aff id="N0x98a91e0.0x9eb80d0">Institute for Neuroscience, Carleton University, Ottawa, ON, Canada K1H 6N5;</nlm:aff>
<country>Canada</country>
<wicri:regionArea>Institute for Neuroscience, Carleton University, Ottawa, ON</wicri:regionArea>
<wicri:noRegion>ON</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Park, David S" sort="Park, David S" uniqKey="Park D" first="David S." last="Park">David S. Park</name>
<affiliation wicri:level="1"><nlm:aff id="N0x98a91e0.0x9eb80d0">Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON, Canada K1H 8M5;</nlm:aff>
<country>Canada</country>
<wicri:regionArea>Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON</wicri:regionArea>
<wicri:noRegion>ON</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Mak, Tak W" sort="Mak, Tak W" uniqKey="Mak T" first="Tak W." last="Mak">Tak W. Mak</name>
<affiliation wicri:level="4"><nlm:aff id="N0x98a91e0.0x9eb80d0">Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada M5G 2C1;</nlm:aff>
<country>Canada</country>
<wicri:regionArea>Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">15784737</idno>
<idno type="pmc">555037</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC555037</idno>
<idno type="RBID">PMC:555037</idno>
<idno type="doi">10.1073/pnas.0501282102</idno>
<date when="2005">2005</date>
<idno type="wicri:Area/Pmc/Corpus">000319</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000319</idno>
<idno type="wicri:Area/Pmc/Curation">000319</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000319</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000C42</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000C42</idno>
<idno type="wicri:source">PubMed</idno>
<idno type="wicri:Area/PubMed/Corpus">001272</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001272</idno>
<idno type="wicri:Area/PubMed/Curation">001272</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001272</idno>
<idno type="wicri:Area/PubMed/Checkpoint">001272</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001272</idno>
<idno type="wicri:Area/Ncbi/Merge">000519</idno>
<idno type="wicri:Area/Ncbi/Curation">000519</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">000519</idno>
<idno type="wicri:doubleKey">0027-8424:2005:Kim R:hypersensitivity:of:dj</idno>
<idno type="wicri:Area/Main/Merge">002D00</idno>
<idno type="wicri:Area/Main/Curation">002980</idno>
<idno type="wicri:Area/Main/Exploration">002980</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress</title>
<author><name sortKey="Kim, Raymond H" sort="Kim, Raymond H" uniqKey="Kim R" first="Raymond H." last="Kim">Raymond H. Kim</name>
<affiliation wicri:level="4"><nlm:aff id="N0x98a91e0.0x9eb80d0">Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada M5G 2C1;</nlm:aff>
<country>Canada</country>
<wicri:regionArea>Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Smith, Patrice D" sort="Smith, Patrice D" uniqKey="Smith P" first="Patrice D." last="Smith">Patrice D. Smith</name>
<affiliation wicri:level="1"><nlm:aff id="N0x98a91e0.0x9eb80d0">Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON, Canada K1H 8M5;</nlm:aff>
<country>Canada</country>
<wicri:regionArea>Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON</wicri:regionArea>
<wicri:noRegion>ON</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Aleyasin, Hossein" sort="Aleyasin, Hossein" uniqKey="Aleyasin H" first="Hossein" last="Aleyasin">Hossein Aleyasin</name>
<affiliation wicri:level="1"><nlm:aff id="N0x98a91e0.0x9eb80d0">Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON, Canada K1H 8M5;</nlm:aff>
<country>Canada</country>
<wicri:regionArea>Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON</wicri:regionArea>
<wicri:noRegion>ON</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hayley, Shawn" sort="Hayley, Shawn" uniqKey="Hayley S" first="Shawn" last="Hayley">Shawn Hayley</name>
<affiliation wicri:level="1"><nlm:aff id="N0x98a91e0.0x9eb80d0">Institute for Neuroscience, Carleton University, Ottawa, ON, Canada K1H 6N5;</nlm:aff>
<country>Canada</country>
<wicri:regionArea>Institute for Neuroscience, Carleton University, Ottawa, ON</wicri:regionArea>
<wicri:noRegion>ON</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Mount, Matthew P" sort="Mount, Matthew P" uniqKey="Mount M" first="Matthew P." last="Mount">Matthew P. Mount</name>
<affiliation wicri:level="1"><nlm:aff id="N0x98a91e0.0x9eb80d0">Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON, Canada K1H 8M5;</nlm:aff>
<country>Canada</country>
<wicri:regionArea>Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON</wicri:regionArea>
<wicri:noRegion>ON</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Pownall, Scott" sort="Pownall, Scott" uniqKey="Pownall S" first="Scott" last="Pownall">Scott Pownall</name>
<affiliation wicri:level="1"><nlm:aff id="N0x98a91e0.0x9eb80d0">enGene Incorporated, Vancouver, BC, Canada V6T 1Z3;</nlm:aff>
<country>Canada</country>
<wicri:regionArea>enGene Incorporated, Vancouver, BC</wicri:regionArea>
<wicri:noRegion>BC</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wakeham, Andrew" sort="Wakeham, Andrew" uniqKey="Wakeham A" first="Andrew" last="Wakeham">Andrew Wakeham</name>
<affiliation wicri:level="4"><nlm:aff id="N0x98a91e0.0x9eb80d0">Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada M5G 2C1;</nlm:aff>
<country>Canada</country>
<wicri:regionArea>Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="You Ten, Annick J" sort="You Ten, Annick J" uniqKey="You Ten A" first="Annick J." last="You-Ten">Annick J. You-Ten</name>
<affiliation wicri:level="4"><nlm:aff id="N0x98a91e0.0x9eb80d0">Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada M5G 2C1;</nlm:aff>
<country>Canada</country>
<wicri:regionArea>Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kalia, Suneil K" sort="Kalia, Suneil K" uniqKey="Kalia S" first="Suneil K." last="Kalia">Suneil K. Kalia</name>
<affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="N0x98a91e0.0x9eb80d0">Division of Applied and Interventional Research, Toronto Western Hospital Research Institute, Toronto, ON, Canada M5T 2S8</nlm:aff>
<country>Canada</country>
<wicri:regionArea>Division of Applied and Interventional Research, Toronto Western Hospital Research Institute, Toronto, ON</wicri:regionArea>
<wicri:noRegion>ON</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Horne, Patrick" sort="Horne, Patrick" uniqKey="Horne P" first="Patrick" last="Horne">Patrick Horne</name>
<affiliation wicri:level="4"><nlm:aff id="N0x98a91e0.0x9eb80d0">Center for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada M5S 3H2</nlm:aff>
<country>Canada</country>
<wicri:regionArea>Center for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Westaway, David" sort="Westaway, David" uniqKey="Westaway D" first="David" last="Westaway">David Westaway</name>
<affiliation wicri:level="4"><nlm:aff id="N0x98a91e0.0x9eb80d0">Center for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada M5S 3H2</nlm:aff>
<country>Canada</country>
<wicri:regionArea>Center for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lozano, Andres M" sort="Lozano, Andres M" uniqKey="Lozano A" first="Andres M." last="Lozano">Andres M. Lozano</name>
<affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="N0x98a91e0.0x9eb80d0">Division of Applied and Interventional Research, Toronto Western Hospital Research Institute, Toronto, ON, Canada M5T 2S8</nlm:aff>
<country>Canada</country>
<wicri:regionArea>Division of Applied and Interventional Research, Toronto Western Hospital Research Institute, Toronto, ON</wicri:regionArea>
<wicri:noRegion>ON</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Anisman, Hymie" sort="Anisman, Hymie" uniqKey="Anisman H" first="Hymie" last="Anisman">Hymie Anisman</name>
<affiliation wicri:level="1"><nlm:aff id="N0x98a91e0.0x9eb80d0">Institute for Neuroscience, Carleton University, Ottawa, ON, Canada K1H 6N5;</nlm:aff>
<country>Canada</country>
<wicri:regionArea>Institute for Neuroscience, Carleton University, Ottawa, ON</wicri:regionArea>
<wicri:noRegion>ON</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Park, David S" sort="Park, David S" uniqKey="Park D" first="David S." last="Park">David S. Park</name>
<affiliation wicri:level="1"><nlm:aff id="N0x98a91e0.0x9eb80d0">Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON, Canada K1H 8M5;</nlm:aff>
<country>Canada</country>
<wicri:regionArea>Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON</wicri:regionArea>
<wicri:noRegion>ON</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Mak, Tak W" sort="Mak, Tak W" uniqKey="Mak T" first="Tak W." last="Mak">Tak W. Mak</name>
<affiliation wicri:level="4"><nlm:aff id="N0x98a91e0.0x9eb80d0">Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada M5G 2C1;</nlm:aff>
<country>Canada</country>
<wicri:regionArea>Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title>
<idno type="ISSN">0027-8424</idno>
<idno type="eISSN">1091-6490</idno>
<imprint><date when="2005">2005</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Base Sequence</term>
<term>Cell Death</term>
<term>Corpus Striatum (drug effects)</term>
<term>Corpus Striatum (metabolism)</term>
<term>Corpus Striatum (pathology)</term>
<term>DNA, Complementary (genetics)</term>
<term>Denervation</term>
<term>Gene Targeting</term>
<term>Humans</term>
<term>Intracellular Signaling Peptides and Proteins</term>
<term>MPTP Poisoning (metabolism)</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Mice, Knockout</term>
<term>Motor Activity</term>
<term>Neurons (cytology)</term>
<term>Neurons (metabolism)</term>
<term>Oncogene Proteins (deficiency)</term>
<term>Oncogene Proteins (genetics)</term>
<term>Oncogene Proteins (metabolism)</term>
<term>Oxidative Stress</term>
<term>Parkinson Disease (genetics)</term>
<term>Parkinson Disease (metabolism)</term>
<term>Parkinsonian Disorders (genetics)</term>
<term>Parkinsonian Disorders (metabolism)</term>
<term>Parkinsonian Disorders (physiopathology)</term>
<term>Protein Deglycase DJ-1</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="deficiency" xml:lang="en"><term>Oncogene Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>DNA, Complementary</term>
<term>Oncogene Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Neurons</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Corpus Striatum</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Parkinson Disease</term>
<term>Parkinsonian Disorders</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Corpus Striatum</term>
<term>MPTP Poisoning</term>
<term>Neurons</term>
<term>Oncogene Proteins</term>
<term>Parkinson Disease</term>
<term>Parkinsonian Disorders</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Corpus Striatum</term>
</keywords>
<keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Parkinsonian Disorders</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Base Sequence</term>
<term>Cell Death</term>
<term>Denervation</term>
<term>Gene Targeting</term>
<term>Humans</term>
<term>Intracellular Signaling Peptides and Proteins</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Mice, Knockout</term>
<term>Motor Activity</term>
<term>Oxidative Stress</term>
<term>Protein Deglycase DJ-1</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Mutations of the <italic>DJ-1</italic>
 (PARK7) gene are linked to familial Parkinson's disease. We used gene targeting to generate DJ-1-deficient mice that were viable, fertile, and showed no gross anatomical or neuronal abnormalities. Dopaminergic neuron numbers in the <italic>substantia nigra</italic>
 and fiber densities and dopamine levels in the striatum were normal. However, DJ-1–/– mice showed hypolocomotion when subjected to amphetamine challenge and increased striatal denervation and dopaminergic neuron loss induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine. DJ-1–/–embryonic cortical neurons showed increased sensitivity to oxidative, but not nonoxidative, insults. Restoration of DJ-1 expression to DJ-1–/– mice or cells via adenoviral vector delivery mitigated all phenotypes. WT mice that received adenoviral delivery of DJ-1 resisted 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine-induced striatal damage, and neurons overexpressing DJ-1 were protected from oxidative stress <italic>in vitro</italic>
. Thus, DJ-1 protects against neuronal oxidative stress, and loss of DJ-1 may lead to Parkinson's disease by conferring hypersensitivity to dopaminergic insults.</p>
</div>
</front>
</TEI>
<affiliations><list><country><li>Canada</li>
</country>
<region><li>Ontario</li>
</region>
<settlement><li>Toronto</li>
</settlement>
<orgName><li>Université de Toronto</li>
</orgName>
</list>
<tree><country name="Canada"><region name="Ontario"><name sortKey="Kim, Raymond H" sort="Kim, Raymond H" uniqKey="Kim R" first="Raymond H." last="Kim">Raymond H. Kim</name>
</region>
<name sortKey="Aleyasin, Hossein" sort="Aleyasin, Hossein" uniqKey="Aleyasin H" first="Hossein" last="Aleyasin">Hossein Aleyasin</name>
<name sortKey="Anisman, Hymie" sort="Anisman, Hymie" uniqKey="Anisman H" first="Hymie" last="Anisman">Hymie Anisman</name>
<name sortKey="Hayley, Shawn" sort="Hayley, Shawn" uniqKey="Hayley S" first="Shawn" last="Hayley">Shawn Hayley</name>
<name sortKey="Horne, Patrick" sort="Horne, Patrick" uniqKey="Horne P" first="Patrick" last="Horne">Patrick Horne</name>
<name sortKey="Kalia, Suneil K" sort="Kalia, Suneil K" uniqKey="Kalia S" first="Suneil K." last="Kalia">Suneil K. Kalia</name>
<name sortKey="Lozano, Andres M" sort="Lozano, Andres M" uniqKey="Lozano A" first="Andres M." last="Lozano">Andres M. Lozano</name>
<name sortKey="Mak, Tak W" sort="Mak, Tak W" uniqKey="Mak T" first="Tak W." last="Mak">Tak W. Mak</name>
<name sortKey="Mount, Matthew P" sort="Mount, Matthew P" uniqKey="Mount M" first="Matthew P." last="Mount">Matthew P. Mount</name>
<name sortKey="Park, David S" sort="Park, David S" uniqKey="Park D" first="David S." last="Park">David S. Park</name>
<name sortKey="Pownall, Scott" sort="Pownall, Scott" uniqKey="Pownall S" first="Scott" last="Pownall">Scott Pownall</name>
<name sortKey="Smith, Patrice D" sort="Smith, Patrice D" uniqKey="Smith P" first="Patrice D." last="Smith">Patrice D. Smith</name>
<name sortKey="Wakeham, Andrew" sort="Wakeham, Andrew" uniqKey="Wakeham A" first="Andrew" last="Wakeham">Andrew Wakeham</name>
<name sortKey="Westaway, David" sort="Westaway, David" uniqKey="Westaway D" first="David" last="Westaway">David Westaway</name>
<name sortKey="You Ten, Annick J" sort="You Ten, Annick J" uniqKey="You Ten A" first="Annick J." last="You-Ten">Annick J. You-Ten</name>
</country>
</tree>
</affiliations>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Wicri/Canada/explor/ParkinsonCanadaV1/Data/Main/Exploration

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002980 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 002980 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Wicri/Canada
   |area=    ParkinsonCanadaV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     PMC:555037
   |texte=   Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i   -Sk "pubmed:15784737" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd   \
       | NlmPubMed2Wicri -a ParkinsonCanadaV1

This area was generated with Dilib version V0.6.29.
Data generation: Thu May 4 22:20:19 2017. Site generation: Fri Dec 23 23:17:26 2022

La maladie de Parkinson au Canada (serveur d'exploration)

Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress

Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress

Source :

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki

	La maladie de Parkinson au Canada (serveur d'exploration)
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.