The MAPK/JNK signalling pathway offers potential therapeutic targets for the prevention of acquired deafness.
The c-Jun N-terminal kinases (JNKs) are also called stress activated protein kinases (SAPKs) and 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 of oxidative stress-damaged cells in both the brain and the mammalian inner ear following a trauma. The activation of the inducible transcription factor c-Jun by N-terminal phosphorylation is a central event in JNK-mediated apoptosis of oxidative stress-damaged auditory hair cells following exposure to either acoustic trauma or a toxic level of an aminoglycoside antibiotic and also the apoptosis of auditory neurons as a consequence of a loss of the trophic support provided by the auditory hair cells. In this review, we summarise what is known about the expression and activation of G-proteins, JNKs, c-Jun and c-Fos under oxidative stress conditions within the mammalian cochlea. A particular focus is put on a new peptide conjugate that is a promising protective agent(s) and pharmacological strategies for preventing cochlear damage induced by both acoustic trauma and aminoglycoside ototoxic damage.
Zine
A
A
Université de Montpellier I, INSERM U.583, Physiopathologie et Thérapie des déficits sensoriels et moteurs, 34090, France. zine@montp.inserm.fr
van de Water
T R
TR
D000617:Aminoglycosides / Q000037:antagonists & inhibitors / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D003638:Deafness / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D009410:Nerve Degeneration / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D009622:Noise / Q000009:adverse effects; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use
D000617:Aminoglycosides; D010455:Peptides; C478085:D-JNKI-1