JNK-mediated induction of cyclooxygenase 2 is required for neurodegeneration in a mouse model of Parkinson's disease
Identifieur interne : 000409 ( Ncbi/Checkpoint ); précédent : 000408; suivant : 000410JNK-mediated induction of cyclooxygenase 2 is required for neurodegeneration in a mouse model of Parkinson's disease
Auteurs : Stéphane Hunot ; Miquel Vila ; Peter Teismann ; Roger J. Davis [États-Unis] ; Etienne C. Hirsch ; Serge Przedborski [États-Unis] ; Pasko Rakic [États-Unis] ; Richard A. FlavellSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2004.
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopamine-containing neurons, but the molecular pathways underlying its pathogenesis remain uncertain. Here, we show that by eliminating c-Jun N-terminal kinases (JNKs) we can prevent neurodegeneration and improve motor function in an animal model of PD. First, we found that c-Jun is activated in dopaminergic neurons from PD patients and in the 1-methyl-4-phenyl-1,2,4,6-tetrahydropyridine (MPTP) mouse model of PD. Examination of various JNK-deficient mice shows that both JNK2 and JNK3, but not JNK1, are required for MPTP-induced c-Jun activation and dopaminergic cell demise. Furthermore, we have identified cyclooxygenase (COX) 2 as a molecular target of JNK activation and demonstrated that COX-2 is indispensable for MPTP-induced dopaminergic cell death. Our data revealed that JNK2- and JNK3-induced COX-2 may be a principle pathway responsible for neurodegeneration in PD.
Url:
DOI: 10.1073/pnas.0307453101
PubMed: 14704277
PubMed Central: 327205
Affiliations:
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Flavell</name><affiliation><nlm:aff id="N0x8d186f0.0x8a8d538">Section of Immunobiology,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="N0x8d186f0.0x8a8d538">Howard Hughes Medical Institute</nlm:aff></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="2004">2004</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopamine-containing neurons, but the molecular pathways underlying its pathogenesis remain uncertain. Here, we show that by eliminating c-Jun N-terminal kinases (JNKs) we can prevent neurodegeneration and improve motor function in an animal model of PD. First, we found that c-Jun is activated in dopaminergic neurons from PD patients and in the 1-methyl-4-phenyl-1,2,4,6-tetrahydropyridine (MPTP) mouse model of PD. Examination of various JNK-deficient mice shows that both JNK2 and JNK3, but not JNK1, are required for MPTP-induced c-Jun activation and dopaminergic cell demise. Furthermore, we have identified cyclooxygenase (COX) 2 as a molecular target of JNK activation and demonstrated that COX-2 is indispensable for MPTP-induced dopaminergic cell death. Our data revealed that JNK2- and JNK3-induced COX-2 may be a principle pathway responsible for neurodegeneration in PD.</p></div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Connecticut</li><li>Massachusetts</li><li>État de New York</li></region></list><tree><noCountry><name sortKey="Flavell, Richard A" sort="Flavell, Richard A" uniqKey="Flavell R" first="Richard A." last="Flavell">Richard A. Flavell</name><name sortKey="Hirsch, Etienne C" sort="Hirsch, Etienne C" uniqKey="Hirsch E" first="Etienne C." last="Hirsch">Etienne C. Hirsch</name><name sortKey="Hunot, Stephane" sort="Hunot, Stephane" uniqKey="Hunot S" first="Stéphane" last="Hunot">Stéphane Hunot</name><name sortKey="Teismann, Peter" sort="Teismann, Peter" uniqKey="Teismann P" first="Peter" last="Teismann">Peter Teismann</name><name sortKey="Vila, Miquel" sort="Vila, Miquel" uniqKey="Vila M" first="Miquel" last="Vila">Miquel Vila</name></noCountry><country name="États-Unis"><region name="Massachusetts"><name sortKey="Davis, Roger J" sort="Davis, Roger J" uniqKey="Davis R" first="Roger J." last="Davis">Roger J. Davis</name></region><name sortKey="Przedborski, Serge" sort="Przedborski, Serge" uniqKey="Przedborski S" first="Serge" last="Przedborski">Serge Przedborski</name><name sortKey="Rakic, Pasko" sort="Rakic, Pasko" uniqKey="Rakic P" first="Pasko" last="Rakic">Pasko Rakic</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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