Blocking pro-cell-death signal pathways to conserve hearing

Christine T Dinh, Thomas R Van De Water

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The programmed cell death of stress-damaged auditory hair cells can occur through a variety of signal pathways, and therapeutic modalities that block pro-cell-death pathways are being developed and evaluated for hearing preservation. Because of their ability to have both anti-inflammatory and anti-apoptotic actions, corticosteroids have long been used to protect against several types of acute sensorineural hearing loss. Other anti-apoptotic drugs that target the mitogen-activated protein kinase (MAPK)/c-Jun-N terminal kinase (JNK) signal cascade, such as D-JNKI-1 (AM-111) and SP600125, have produced promising results both in vitro and in laboratory animal studies, with AM-111 showing promise in preliminary clinical trials. Antioxidant drugs, e.g. sodium thiosulfate, N-acetylcysteine, and D-methionine, have been shown in animal studies to attenuate permanent threshold shifts in hearing by reducing oxidative stress. In addition to reviewing selected therapeutic trends for the conservation of hearing, we review our experiences with dexamethasone and D-JNKI-1 and report results from our current research.

Original languageEnglish
Pages (from-to)383-392
Number of pages10
JournalAudiology and Neurotology
Volume14
Issue number6
DOIs
StatePublished - Nov 1 2009

Fingerprint

Hearing
Signal Transduction
Cell Death
Auditory Hair Cells
Aptitude
JNK Mitogen-Activated Protein Kinases
Sensorineural Hearing Loss
Acetylcysteine
Laboratory Animals
Mitogen-Activated Protein Kinases
Pharmaceutical Preparations
Methionine
Dexamethasone
Adrenal Cortex Hormones
Oxidative Stress
Anti-Inflammatory Agents
Antioxidants
Clinical Trials
D-JNKI-1
Therapeutics

Keywords

  • Antioxidants
  • Apoptosis
  • Cochlea
  • Corticosteroids
  • Hearing loss
  • JNK inhibitors

ASJC Scopus subject areas

  • Physiology
  • Otorhinolaryngology
  • Sensory Systems
  • Speech and Hearing

Cite this

Blocking pro-cell-death signal pathways to conserve hearing. / Dinh, Christine T; Van De Water, Thomas R.

In: Audiology and Neurotology, Vol. 14, No. 6, 01.11.2009, p. 383-392.

Research output: Contribution to journalArticle

Dinh, Christine T ; Van De Water, Thomas R. / Blocking pro-cell-death signal pathways to conserve hearing. In: Audiology and Neurotology. 2009 ; Vol. 14, No. 6. pp. 383-392.
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