Molecular mechanisms of cell death in the ear.

Damage to sensory cells and neurones of the inner ear, induced by ototoxic drugs, physical stimulation, or even normal aging, occurs by mechanisms that are not yet fully elucidated. However, for the individual the consequent loss of hearing can be devastating. This the concept that, in some instances, this brain cell death may be preventable has provided an exciting and novel route to thwart the degenerative process. Signals that trigger cell death can be as diverse as the removal of essential growth factors, damage by exogenous toxins (including ototoxic drugs), free radicals, and excitotoxins. An important facet to the newly discovered death cascade is that it can be halted, and such interventions may rescue the dying cell. The question now remains whether any of the cell death observed on ototoxic or noise-induced hearing loss occurs by an "active" programmed mechanism (apoptosis), as physiological cell death does in the developing ear, and if so, whether it can be prevented.