Canonical MAPK signaling in auditory neuropathy

Auditory neuropathy (AN) is an under-recognized form of hearing loss characterized by lesions in inner hair cells (IHCs), ribbon synapses and spiral ganglion neurons (SGNs). The lack of a targeted therapy for AN has increased the need for a better understanding of the pathogenic mechanism of AN. As mitogen-activated protein kinase (MAPK) signaling is ubiquitous in many biological processes, its alteration may facilitate the pathogenesis of multiple sites in AN. Here, we summaries the characteristics of AN under different molecular bases and first explore the mechanism of MAPK at different lesion sites. Alterations of extracellular signal-regulated kinase (ERK)/MAPK occur in IHCs and SGNs, whereas modulations of p38 and c-Jun NH2-terminal kinase (JNK) were found in ribbon synapses and SGNs. In conclusion, inductive MAPK alterations in the pathogenesis and development of AN are likely to represent a potential therapeutic target to guide the development of treatments.