title: JNK inhibition as a potential strategy in treating Parkinson's disease.
abstract: Parkinson's disease is characterized by the pathological loss of dopaminergic neurons in the substantia nigra. The current therapy for Parkinson's disease is aimed to replace the lost transmitter. But the ultimate objective in the neurodegenerative therapy is the functional restoration and/or cessation of progression of neuronal loss. Given the critical role that the c-Jun N-terminal kinase (JNK) pathway plays in regulating the cellular processes that are involved in Parkinson's disease, the importance of JNK in this disease's pathogenesis is being increasingly recognized. Much evidence suggests that JNK plays an important role in mediating 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/1-methyl-4-phenylpyridnium ion (MPP(+))-induced neurotoxicity. Therefore, direct blockade of JNK may prevent or effectively slow the progression of Parkinson's disease. Studies including our own showed that the inhibition of JNK with SP-600125, a specific inhibitor of JNK, protects dopaminergic neurons both from MPP(+)-induced neuronal apoptosis in vitro and in MPTP Parkinson's disease model. These results support JNK inhibition as a potential strategy in treating Parkinson's disease.
authors.affiliation: Department of Pharmacology, Zhongshan Medical College, Sun Yat-sen University, Guangzhou 510089, China.
authors.forename: Wenya
authors.initials: W
authors.lastname: Wang
authors.forename: Chi
authors.initials: C
authors.lastname: Ma
authors.forename: Zixu
authors.initials: Z
authors.lastname: Mao
authors.forename: Mingtao
authors.initials: M
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D020267:MPTP Poisoning; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D015398:Signal Transduction
chemical_list: D004791:Enzyme Inhibitors; D048031:JNK Mitogen-Activated Protein Kinases