Activation of the c-Jun N terminal kinase pathway in an animal model of Parkinson's disease.
In neuronal stress and degeneration, mitogen-activated protein (MAP) kinase signaling pathways play an important role. We studied the pattern of activation of the c-Jun N terminal kinase (JNK) signal transduction pathway during the course of a subacute MPTP mouse model of Parkinson's disease. In this model, there was no significant neuronal loss, but the function of the dopaminergic neurons was significantly decreased. During MPTP administration, phosphorylation of p-Jun was increased in the substantia nigra, and MKK4 was increased both in the striatum and substantia nigra. We conclude that after MPTP intoxication in the mouse, activation of the JNK pathway occurs both in the striatum and in the substantia nigra. This activation does not seem to corrrelate with loss of neuronal cell bodies but might represent a response to damage/loss of axonal terminals.
Willesen
Mette Georgi
MG
Department of Neurodegenerative Disorders, H. Lundbeck A/S, Valby, Denmark. mgw@lundbeck.com
Gammeltoft
Steen
S
Vaudano
Elisabetta
E
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D048031:JNK Mitogen-Activated Protein Kinases; D008636:Mesencephalon / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology; D015398:Signal Transduction
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases