Defective Fas expression exacerbates neurotoxicity in a model of Parkinson's disease
Identifieur interne : 002D14 ( Main/Merge ); précédent : 002D13; suivant : 002D15Defective Fas expression exacerbates neurotoxicity in a model of Parkinson's disease
Auteurs : Anne M. Landau [Canada] ; Kelvin C. Luk [Canada] ; Michelle-Lee Jones [Canada] ; Rosmarie Siegrist-Johnstone [Canada] ; Yoon Kow Young [Canada] ; Edouard Kouassi ; Vladimir V. Rymar [Canada] ; Alain Dagher [Canada] ; Abbas F. Sadikot [Canada] ; Julie Desbarats [Canada]Source :
- The Journal of Experimental Medicine [ 0022-1007 ] ; 2005.
English descriptors
- KwdEn :
- Aged, Animals, Antigens, CD95 (metabolism), Brain (pathology), Chromatography, High Pressure Liquid, Female, Flow Cytometry, Humans, Immunohistochemistry, Lymphoproliferative Disorders (metabolism), MPTP Poisoning (metabolism), Male, Mice, Mice, Mutant Strains, Middle Aged, Neurons (metabolism), Parkinson Disease (metabolism), Signal Transduction (physiology), Up-Regulation.
- MESH :
- chemical , metabolism : Antigens, CD95.
- metabolism : Lymphoproliferative Disorders, MPTP Poisoning, Neurons, Parkinson Disease.
- pathology : Brain.
- physiology : Signal Transduction.
- Aged, Animals, Chromatography, High Pressure Liquid, Female, Flow Cytometry, Humans, Immunohistochemistry, Male, Mice, Mice, Mutant Strains, Middle Aged, Up-Regulation.
Abstract
Fas (CD95), a member of the tumor necrosis factor-receptor superfamily, has been studied extensively as a death-inducing receptor in the immune system. However, Fas is also widely expressed in a number of other tissues, including in neurons. Here, we report that defects in the Fas/Fas ligand system unexpectedly render mice highly susceptible to neural degeneration in a model of Parkinson's disease. We found that Fas-deficient lymphoproliferative mice develop a dramatic phenotype resembling clinical Parkinson's disease, characterized by extensive nigrostriatal degeneration accompanied by tremor, hypokinesia, and loss of motor coordination, when treated with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at a dose that causes no neural degeneration or behavioral impairment in WT mice. Mice with generalized lymphoproliferative disease, which express a mutated Fas ligand, display an intermediate phenotype between that of lymphoproliferative and WT mice. Moreover, Fas engagement directly protects neuronal cells from MPTP/1-methyl-4-phenylpyridinium ion toxicity in vitro. Our data show that decreased Fas expression renders dopaminergic neurons highly susceptible to degeneration in response to a Parkinson-causing neurotoxin. These findings constitute the first evidence for a neuroprotective role for Fas in vivo.
Url:
DOI: 10.1084/jem.20050163
PubMed: 16129703
PubMed Central: 2212882
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000336
- to stream Pmc, to step Curation: 000336
- to stream Pmc, to step Checkpoint: 000C43
- to stream PubMed, to step Corpus: 001235
- to stream PubMed, to step Curation: 001235
- to stream PubMed, to step Checkpoint: 001235
- to stream Ncbi, to step Merge: 000570
- to stream Ncbi, to step Curation: 000570
- to stream Ncbi, to step Checkpoint: 000570
Links to Exploration step
PMC:2212882Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Defective Fas expression exacerbates neurotoxicity in a model of Parkinson's disease</title><author><name sortKey="Landau, Anne M" sort="Landau, Anne M" uniqKey="Landau A" first="Anne M." last="Landau">Anne M. Landau</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Physiology, McGill University, Montreal, Quebec, Canada, H3G 1Y6</nlm:aff><orgName type="university">Université McGill</orgName><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Luk, Kelvin C" sort="Luk, Kelvin C" uniqKey="Luk K" first="Kelvin C." last="Luk">Kelvin C. Luk</name><affiliation wicri:level="4"><nlm:aff id="aff2">Division of Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada, H3A 2B4</nlm:aff><orgName type="university">Université McGill</orgName><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Jones, Michelle Lee" sort="Jones, Michelle Lee" uniqKey="Jones M" first="Michelle-Lee" last="Jones">Michelle-Lee Jones</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Physiology, McGill University, Montreal, Quebec, Canada, H3G 1Y6</nlm:aff><orgName type="university">Université McGill</orgName><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Siegrist Johnstone, Rosmarie" sort="Siegrist Johnstone, Rosmarie" uniqKey="Siegrist Johnstone R" first="Rosmarie" last="Siegrist-Johnstone">Rosmarie Siegrist-Johnstone</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Physiology, McGill University, Montreal, Quebec, Canada, H3G 1Y6</nlm:aff><orgName type="university">Université McGill</orgName><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Young, Yoon Kow" sort="Young, Yoon Kow" uniqKey="Young Y" first="Yoon Kow" last="Young">Yoon Kow Young</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Physiology, McGill University, Montreal, Quebec, Canada, H3G 1Y6</nlm:aff><orgName type="university">Université McGill</orgName><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Kouassi, Edouard" sort="Kouassi, Edouard" uniqKey="Kouassi E" first="Edouard" last="Kouassi">Edouard Kouassi</name><affiliation><nlm:aff id="aff4">Guy-Bernier Research Center, Maisonneuve-Rosemont Hospital</nlm:aff><wicri:noCountry code="subfield">Maisonneuve-Rosemont Hospital</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff5">Department of Medicine, University of Montreal, Montreal, Quebec, Canada, H1T 2M4</nlm:aff><wicri:noCountry code="subfield">H1T 2M4</wicri:noCountry></affiliation></author><author><name sortKey="Rymar, Vladimir V" sort="Rymar, Vladimir V" uniqKey="Rymar V" first="Vladimir V." last="Rymar">Vladimir V. Rymar</name><affiliation wicri:level="4"><nlm:aff id="aff2">Division of Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada, H3A 2B4</nlm:aff><orgName type="university">Université McGill</orgName><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Dagher, Alain" sort="Dagher, Alain" uniqKey="Dagher A" first="Alain" last="Dagher">Alain Dagher</name><affiliation wicri:level="4"><nlm:aff id="aff3">McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada, H3A 2B4</nlm:aff><orgName type="university">Université McGill</orgName><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Sadikot, Abbas F" sort="Sadikot, Abbas F" uniqKey="Sadikot A" first="Abbas F." last="Sadikot">Abbas F. Sadikot</name><affiliation wicri:level="4"><nlm:aff id="aff2">Division of Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada, H3A 2B4</nlm:aff><orgName type="university">Université McGill</orgName><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Desbarats, Julie" sort="Desbarats, Julie" uniqKey="Desbarats J" first="Julie" last="Desbarats">Julie Desbarats</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Physiology, McGill University, Montreal, Quebec, Canada, H3G 1Y6</nlm:aff><orgName type="university">Université McGill</orgName><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">16129703</idno><idno type="pmc">2212882</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212882</idno><idno type="RBID">PMC:2212882</idno><idno type="doi">10.1084/jem.20050163</idno><date when="2005">2005</date><idno type="wicri:Area/Pmc/Corpus">000336</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000336</idno><idno type="wicri:Area/Pmc/Curation">000336</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000336</idno><idno type="wicri:Area/Pmc/Checkpoint">000C43</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000C43</idno><idno type="wicri:source">PubMed</idno><idno type="wicri:Area/PubMed/Corpus">001235</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001235</idno><idno type="wicri:Area/PubMed/Curation">001235</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001235</idno><idno type="wicri:Area/PubMed/Checkpoint">001235</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001235</idno><idno type="wicri:Area/Ncbi/Merge">000570</idno><idno type="wicri:Area/Ncbi/Curation">000570</idno><idno type="wicri:Area/Ncbi/Checkpoint">000570</idno><idno type="wicri:doubleKey">0022-1007:2005:Landau A:defective:fas:expression</idno><idno type="wicri:Area/Main/Merge">002D14</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Defective Fas expression exacerbates neurotoxicity in a model of Parkinson's disease</title><author><name sortKey="Landau, Anne M" sort="Landau, Anne M" uniqKey="Landau A" first="Anne M." last="Landau">Anne M. Landau</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Physiology, McGill University, Montreal, Quebec, Canada, H3G 1Y6</nlm:aff><orgName type="university">Université McGill</orgName><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Luk, Kelvin C" sort="Luk, Kelvin C" uniqKey="Luk K" first="Kelvin C." last="Luk">Kelvin C. Luk</name><affiliation wicri:level="4"><nlm:aff id="aff2">Division of Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada, H3A 2B4</nlm:aff><orgName type="university">Université McGill</orgName><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Jones, Michelle Lee" sort="Jones, Michelle Lee" uniqKey="Jones M" first="Michelle-Lee" last="Jones">Michelle-Lee Jones</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Physiology, McGill University, Montreal, Quebec, Canada, H3G 1Y6</nlm:aff><orgName type="university">Université McGill</orgName><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Siegrist Johnstone, Rosmarie" sort="Siegrist Johnstone, Rosmarie" uniqKey="Siegrist Johnstone R" first="Rosmarie" last="Siegrist-Johnstone">Rosmarie Siegrist-Johnstone</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Physiology, McGill University, Montreal, Quebec, Canada, H3G 1Y6</nlm:aff><orgName type="university">Université McGill</orgName><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Young, Yoon Kow" sort="Young, Yoon Kow" uniqKey="Young Y" first="Yoon Kow" last="Young">Yoon Kow Young</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Physiology, McGill University, Montreal, Quebec, Canada, H3G 1Y6</nlm:aff><orgName type="university">Université McGill</orgName><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Kouassi, Edouard" sort="Kouassi, Edouard" uniqKey="Kouassi E" first="Edouard" last="Kouassi">Edouard Kouassi</name><affiliation><nlm:aff id="aff4">Guy-Bernier Research Center, Maisonneuve-Rosemont Hospital</nlm:aff><wicri:noCountry code="subfield">Maisonneuve-Rosemont Hospital</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff5">Department of Medicine, University of Montreal, Montreal, Quebec, Canada, H1T 2M4</nlm:aff><wicri:noCountry code="subfield">H1T 2M4</wicri:noCountry></affiliation></author><author><name sortKey="Rymar, Vladimir V" sort="Rymar, Vladimir V" uniqKey="Rymar V" first="Vladimir V." last="Rymar">Vladimir V. Rymar</name><affiliation wicri:level="4"><nlm:aff id="aff2">Division of Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada, H3A 2B4</nlm:aff><orgName type="university">Université McGill</orgName><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Dagher, Alain" sort="Dagher, Alain" uniqKey="Dagher A" first="Alain" last="Dagher">Alain Dagher</name><affiliation wicri:level="4"><nlm:aff id="aff3">McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada, H3A 2B4</nlm:aff><orgName type="university">Université McGill</orgName><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Sadikot, Abbas F" sort="Sadikot, Abbas F" uniqKey="Sadikot A" first="Abbas F." last="Sadikot">Abbas F. Sadikot</name><affiliation wicri:level="4"><nlm:aff id="aff2">Division of Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada, H3A 2B4</nlm:aff><orgName type="university">Université McGill</orgName><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Desbarats, Julie" sort="Desbarats, Julie" uniqKey="Desbarats J" first="Julie" last="Desbarats">Julie Desbarats</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Physiology, McGill University, Montreal, Quebec, Canada, H3G 1Y6</nlm:aff><orgName type="university">Université McGill</orgName><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author></analytic><series><title level="j">The Journal of Experimental Medicine</title><idno type="ISSN">0022-1007</idno><idno type="eISSN">1540-9538</idno><imprint><date when="2005">2005</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Animals</term><term>Antigens, CD95 (metabolism)</term><term>Brain (pathology)</term><term>Chromatography, High Pressure Liquid</term><term>Female</term><term>Flow Cytometry</term><term>Humans</term><term>Immunohistochemistry</term><term>Lymphoproliferative Disorders (metabolism)</term><term>MPTP Poisoning (metabolism)</term><term>Male</term><term>Mice</term><term>Mice, Mutant Strains</term><term>Middle Aged</term><term>Neurons (metabolism)</term><term>Parkinson Disease (metabolism)</term><term>Signal Transduction (physiology)</term><term>Up-Regulation</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antigens, CD95</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Lymphoproliferative Disorders</term><term>MPTP Poisoning</term><term>Neurons</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Brain</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Signal Transduction</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Animals</term><term>Chromatography, High Pressure Liquid</term><term>Female</term><term>Flow Cytometry</term><term>Humans</term><term>Immunohistochemistry</term><term>Male</term><term>Mice</term><term>Mice, Mutant Strains</term><term>Middle Aged</term><term>Up-Regulation</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Fas (CD95), a member of the tumor necrosis factor-receptor superfamily, has been studied extensively as a death-inducing receptor in the immune system. However, Fas is also widely expressed in a number of other tissues, including in neurons. Here, we report that defects in the Fas/Fas ligand system unexpectedly render mice highly susceptible to neural degeneration in a model of Parkinson's disease. We found that Fas-deficient lymphoproliferative mice develop a dramatic phenotype resembling clinical Parkinson's disease, characterized by extensive nigrostriatal degeneration accompanied by tremor, hypokinesia, and loss of motor coordination, when treated with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at a dose that causes no neural degeneration or behavioral impairment in WT mice. Mice with generalized lymphoproliferative disease, which express a mutated Fas ligand, display an intermediate phenotype between that of lymphoproliferative and WT mice. Moreover, Fas engagement directly protects neuronal cells from MPTP/1-methyl-4-phenylpyridinium ion toxicity in vitro. Our data show that decreased Fas expression renders dopaminergic neurons highly susceptible to degeneration in response to a Parkinson-causing neurotoxin. These findings constitute the first evidence for a neuroprotective role for Fas in vivo.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Canada/explor/ParkinsonCanadaV1/Data/Main/Merge
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002D14 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Merge/biblio.hfd -nk 002D14 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Canada
|area= ParkinsonCanadaV1
|flux= Main
|étape= Merge
|type= RBID
|clé= PMC:2212882
|texte= Defective Fas expression exacerbates neurotoxicity in a model of Parkinson's disease
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Merge/RBID.i -Sk "pubmed:16129703" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Merge/biblio.hfd \
| NlmPubMed2Wicri -a ParkinsonCanadaV1
| This area was generated with Dilib version V0.6.29. |  |