Targeting the JNK pathway as a therapeutic protective strategy for nervous system diseases.
The c-Jun N-terminal kinases (JNKs) are members of the family of mitogen activated protein kinases (MAPKs). While the functions of the JNKs under physiological conditions are diverse and not completely understood, there is increasing evidence that JNKs are potent effectors of apoptosis in both the brain and the mammalian inner ear following a variety of injuries. The activation of the inducible transcription factor c-Jun by N-terminal phosphorylation is a central event in JNK-mediated neural and inner ear hair cell death. A cell permeable peptide designed specifically to inhibit JNK signaling has proven successful in in vivo models of both neuronal degeneration following cerebral ischemia and auditory hair cell degeneration following exposure to either acoustic trauma or a toxic level of an aminoglycoside antibiotic. Here we discuss the evidence supporting the application of JNK inhibitors to prevent cellular degeneration in several central nervous system (CNS) and peripheral nervous system (PNS) diseases with an emphasis on traumatic ischemic damage to the CNS and acquired deafness in the PNS receptors.
Bonny
Christophe
C
Université de Lausanne, Lausanne, Switzerland.
Borsello
Tiziana
T
Zine
Azel
A
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D003638:Deafness / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000201:enzymology* / Q000517:prevention & control; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000201:enzymology* / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D018696:Neuroprotective Agents; D048031:JNK Mitogen-Activated Protein Kinases