![]() The various cellular molecular pathways are discussed systematically. To summarize the research regarding hearing loss based on cellular molecular pathways in recent years and to guide hearing recovery and the prevention of hearing loss, this paper reviews the current research on the biology of HC damage. Importantly, drug interventions in the majority of these processes can achieve benefit. Among the identified pathways, mitogen-activated protein kinase (MAPK), phosphoinositide-3 kinase/protein kinase B (PI3K/Akt), Notch/Wnt/Atoh1, calcium channel, and oxidative stress/reactive oxygen species (ROS) signaling pathways are the most relevant. As research into the necrobiology of the inner ear progresses, the pathways specific to auditory HC death will become better defined. As research and treatment in this area are critical, research regarding the cellular molecular pathway mechanisms has attracted considerable attention.Īt present, there are an increasing number of studies that have focused on cellular molecular pathways that could represent potential checkpoints in the mechanism of hearing loss and HC damage. However, there is relatively little information about the cellular processes that mediate HC damage. The signaling cascades that occur at the cellular and molecular levels are highly complex and intertwined. These pathways can be proinflammatory, prodeath, and even prosurvival. Several signaling cascades are activated following injury to the cochlea. Middle ear lesions, noise, trauma, and genetic mutations can cause damage to HCs, which ultimately lead to hearing loss. Hearing loss is caused by the irreversible loss of sensory HCs and degeneration of SGNs. ![]() The inner ear and the brain then collaborate to make us feel sound. This is turn causes the deflection of stereocilia on the top surface of IHCs, which opens mechanoelectrical transduction channels located at the tip of the stereocilia, and simultaneously leads to excitation of the SGNs. Vibrations caused by sound are amplified by the three rows of OHCs and subsequently reach the cochlea. The auditory sensory HCs are located in the organ of Corti and include a row of inner hair cells (IHCs), three rows of outer hair cells (OHCs), and supporting cells. Hair cells (HCs) and spiral ganglion neurons (SGNs) are the main structures of sound transmission in the cochlea. Considering that the cochlea is an important sound receiver, analysis of the structure and sound transmission processes of the cochlea form the basis of treatment. SNHL is an etiologically heterogeneous disorder resulting from numerous genetic and environmental factors and is caused by damage to the body’s sound transmission function. ![]() Etiologically, hearing loss can be roughly classified into two categories, including hereditary and nonhereditary. Hearing loss can be divided into three types according to the location of the lesion: conductive hearing loss (CHL), sensorineural hearing loss (SNHL), and mixed hearing loss. These causes determine the specific type of hearing loss and the treatment orientation. Thus far, various causes of hearing loss have been identified and studied, such as aging, ototoxic drugs, genetic mutations of deafness genes, ear or brain tumors, and exposure to loud noises (even for short time). Hearing dysfunction may lead to speech retardation, as well as poor social integration and quality of life. More than 500 million people are affected by this health problem, and 1 in every 500 newborns worldwide is deaf. Globally, hearing loss is the most common sensory disorder, and its severity ranges from mild hearing impairment to total deafness. The molecular interactions of these signaling pathways play an important role in the survival of HCs, which may provide a theoretical basis and possible therapeutic interventions for the treatment of hearing loss. The role of the mitogen-activated protein kinase (MAPK), phosphoinositide-3 kinase/protein kinase B (PI3K/Akt), Notch/Wnt/Atoh1, calcium channels, and oxidative stress/reactive oxygen species (ROS) signaling pathways are the most relevant. In this review, we described and summarized the signaling pathways that regulate the development and survival of auditory HCs in SNHL. As the main sound transmission structure in the cochlea, it is necessary to maintain the normal shape and survival of HCs. The loss of auditory sensory hair cells (HCs) is the most common cause of sensorineural hearing loss (SNHL).
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