Hair cell apoptosis processes

Hair cell apoptosis processes encompass the programmed cell death pathways responsible for the loss of sensory hair cells within the cochlea, which is the hallmark of permanent sensorineural hearing loss. These processes are primarily triggered by acoustic trauma, aging, and the administration of ototoxic medications such as cisplatin or aminoglycoside antibiotics [1, 15]. The molecular cascade involves the activation of the c-Jun N-terminal kinase (JNK) signaling pathway and the accumulation of reactive oxygen species (ROS), which lead to mitochondrial dysfunction and the release of pro-apoptotic factors [5, 8]. This sequence ultimately activates executioner caspases, specifically Caspase-3, which degrade the cell's structural and functional proteins [2, 13]. Therapeutic strategies aim to inhibit these pathways using otoprotective agents such as brimapitide (AM-111), a JNK inhibitor, and arazasetron (SENS-401), which modulates 5-HT3 receptors and calcineurin [1, 6]. Clinical implementation faces challenges including the need for localized drug delivery and the risk of converting apoptosis into necrotic cell death if the inhibition is incomplete or improperly targeted [8, 9].

Other names

Inner ear hair cell apoptosisCochlear hair cell death pathwayProgrammed cell death of hair cellsHair cell programmed cell death

Inhibition of c-Jun N-terminal kinase (JNK) signaling, antagonism of 5-HT3 receptors, calcineurin inhibition, executioner caspase inhibition, and antioxidant-mediated reduction of oxidative stress.