PARP inhibitor rescues hearing and hair cell impairment in Cx26‐null mice

Abstract GJB2 (encoding connexin26, Cx26) mutation is the most common genetic cause of hereditary deafness. Cochlear sensory hair cell (HC) death core pathologic phenomenon ‐related However, mechanism‐based therapy still obscure. A targeted‐cell conditional Gjb2 knockout mouse model was established in which Cx26 Deiters cells and pillar were knocked out at birth. We explored mechanism HC caused by deficiency supporting (SCs), exhibited moderate deafness, early without SCs, a decrease distortion product otoacoustic emission. Here, DNA damage response observed HCs during onset hearing loss. Apoptosis, necroptosis, ferroptosis do not contribute to HCs. identified demonstrated that parthanatos, poly‐(ADP‐ribose) polymerase (PARP)‐dependent caspase‐independent form death, degeneration. Furthermore, we use PARP inhibitors effectively alleviated both deafness Our study reveals specific deficiency. These findings demonstrate targeting parthanatos an protective strategy prevention