Enhancing Cochlear Proteome Fidelity to Prevent Noise-Induced Hearing Loss

The goal of this project is to advance the development of a noninvasive therapeutic strategy to protect US Service members from noise induced hearing loss (NIHL). Recently, it was unexpectedly found that many US service members suffer from NIHL. Although they perform well on auditory detection tasks, their ability to understand speech in noisy environments is degraded. This mysterious phenomenon, now called “hidden hearing loss”, represents a major health crisis since it puts US Service members at an increased risk on the battlefield and reduces their quality of life after returning home. In our preliminary studies on mice, we discovered that exposure to loud noise causes the accumulation of biological molecules (i.e. proteins) within the inner ear immediately after noise exposure. Our results show that this process is due to impaired protein degradation and folding, which induces the selective expression of “protein doctors” that refold and degrade these substrates. In addition, during the recovery period two weeks after noise exposure, we found that the cellular machinery responsible for synthesizing new proteins was also activated. The rational is that drugs that regulate “protein doctor” function can protect the inner ear and prevent NIHL through activation of stress-responsive signaling. Indeed, in our preliminary studies, we have identified several drugs that can protect the cochlea from NIHL.