Specific activities of individual c-Jun N-terminal kinases in the brain.
The c-Jun N-terminal kinases (JNKs) are multifunctional molecules which, on the one hand, regulate various processes in brain development, repair and memory formation. On the other hand, JNKs are potent effectors of neuronal death and neuroinflammation. This review summarizes recent findings on individual JNK functions in the nervous system under pathophysiological conditions and on their regulation by upstream kinases, phosphatases and formation of context-dependent signalosomes. By focusing on different aspects of JNK signaling, it becomes increasingly obvious that the JNK cascade is intricately regulated and intensely dependent on the availability and functionality of its single components and their intracellular localization. Our review also emphasizes, that JNKs are indispensable for neuronal cell death as well as many physiological functions in the brain. Finally, we discuss pharmacological strategies which target pathological JNK activities without affecting their physiological functions.
Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein (UK-SH), Campus Kiel, Hospitalstrasse 4, 24105 Kiel, Germany.
W
W
Haeusgen
R
R
Boehm
Y
Y
Zhao
T
T
Herdegen
V
V
Waetzig
D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000254:growth & development / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D002986:Clinical Trials as Topic; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007858:Learning / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000502:physiology; D008568:Memory / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology; D009474:Neurons / Q000201:enzymology* / Q000502:physiology; D013347:Subcellular Fractions / Q000201:enzymology
D048031:JNK Mitogen-Activated Protein Kinases