Inhibition of the MAPK/JNK signal cascade protects hearing and auditory sensory cells against ototoxins and sound trauma: Can it conserve residual hearing during cochlear implantation?

Thomas R Van De Water, Azel Zine, Adrien Eshraghi, Cai Hong Mou, Jing Wang, Jean Luc Puel, Thomas J. Balkany

Research output: Contribution to journalArticle

Abstract

Pharmacological manipulation of the labyrinth for therapeutic purposes is becoming a reality for the treatment of inner ear disorders. The mitogen-activated protein kinase (MAPK)/c-Jun-N-terminal kinase (JNK) intracellular signal cascade is used by injured auditory sensory cell to initiate their elimination via apoptosis (programmed cell death). This intracellular signal cascade can be inhibited and/or down-regulated by the application of inhibitory peptides and through the use of antisense oligonucleotides directed against specific RNA message sequences. This approach has been shown to be highly effective in preventing the apoptotic cell death of auditory sensory cells that are under oxidative stress because of either ototoxin exposure or exposure to damaging levels of sound. The insertion of an electrode array into the cochlea has been postulated to generate a high level of oxidative stress and to have a progressive component of hearing loss that occurs for several days after the initial electrode insertion. It is probable that this ongoing loss of hearing due to trauma caused by electrode insertion may be preventable and may be due to apoptosis of sensory cells damaged by oxidative stress and signalling via the MAPK/JNK signal cascade. Pharmacological manipulation of the MAPK/JNK signal cascade during cochlear implantation may be an effective therapy for the conservation of residual hearing during and following cochlear implantation. Other promising treatment options include the use of antioxidant molecules, corticosteroids, and blocking antisense oligonucleotides or inhibitory RNAi sequences.

Original languageEnglish (US)
Pages (from-to)72-75
Number of pages4
JournalInternational Congress Series
Volume1273
Issue numberC
DOIs
StatePublished - Nov 1 2004

Keywords

  • Apoptosis
  • Auditory sensory cells
  • Cell death signal cascade
  • Cochlear trauma
  • Oxidative stress
  • Pharmacological treatment

ASJC Scopus subject areas

  • Medicine(all)

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