Molecular Pathways Involved in Apoptotic Cell Death in the Injured Cochlea: Cues to Novel Therapeutic Strategies

Abstract

Most hearing loss results from lesions of the sensory cells and/or neurons of the auditory portion of the inner ear. To date, only the cochlear implantation offers long-term hearing-aid benefit, but still with limited performance and expensive cost. While the underlying causes of deafness are not clear, the death or hair cells and/or neurons and the loss of neuronal contacts are key pathological features. Pinpointing molecular events that control cell death in the cochlea is critical for the development of new strategies to prevent and treat deafness, whether in combination or not with cochlear implant therapy.

Functional Mutation of SMAC/DIABLO, Encoding a Mitochondrial Proapoptotic Protein, Causes Human Progressive Hearing Loss DFNA64

“…5,6 Loss of hair cells, the auditory sensory cells, by apoptosis is a major cause of hearing loss in mammals. [7][8][9] A recent study showed that Bak, a proapoptotic protein, is involved in age-related hearing loss in mice. 10 However, none of the 62 human genes involved in nonsyndromic hearing loss is known to have a proapoptotic function.…”

Apoptotic outer hair cell death in the cochleae of aging Fischer 344/NHsd rats

“…Apoptosis is an energy-dependent process, characterized by a set of unique morphological and biological features (Lallemend et al, 2005; Nicotera et al, 2003; Van De Water et al, 2004). Usami et al (1997) reported the appearance of nuclear DNA fragmentation, a phenotype of apoptosis, in the cochlea of senescence accelerated mice.…”

Loss of function of Ywhah in mice induces deafness and cochlear outer hair cell’s degeneration

“…These results were consistent with the notion that apoptosis is a major cause of hearing loss in mammals. 8 …”