Abstract
Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of doparnine-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.
Original language | English |
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Pages (from-to) | 665-670 |
Number of pages | 5 |
Journal | PNAS |
Volume | 101 |
Issue number | 2 |
Early online date | 2 Jan 2004 |
DOIs | |
Publication status | Published - 13 Jan 2004 |
Keywords
- NF-KAPPA-B
- C-JUN
- DOPAMINERGIC-NEURONS
- INDUCED APOPTOSIS
- GENE-EXPRESSION
- MAP KINASES
- MPTP MODEL
- BRAIN
- CELLS
- PROTEIN