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Proc Natl Acad Sci U S A. 2004 Jan 13;101(2):665-70. Epub 2004 Jan 2.

JNK-mediated induction of cyclooxygenase 2 is required for neurodegeneration in a mouse model of Parkinson's disease.

Author information

1
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.

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.

PMID:
14704277
PMCID:
PMC327205
DOI:
10.1073/pnas.0307453101
[Indexed for MEDLINE]
Free PMC Article

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