Activation of the NRF2 pathway attenuates progression of age-related hearing loss

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16826
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Tohoku University
• Principal Investigator: Honkura Yohei 東北大学, 大学病院, 助教 (20810146)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 難聴 / 内耳 / 酸化ストレス / Nrf2

Outline of Final Research Achievements

Although no prevention or treatments have been established for Age-related hearing loss (AHL), recent studies have suggested that suppression of oxidative stress leads to inhibition of AHL progression. NRF2 is a master transcription factor that regulates various antioxidant proteins and cytoprotection factors. We used one transgenic mice, in which NRF2 is activated. We compared 12-month-old mice. Histological analysis showed that cochlear degeneration was ameliorated in the transgenic mice. Auditory brainstem response thresholds in the transgenic mice were significantly lower than those in the wild type mice. Immunohistochemical analysis suggested that oxidative stress accumulation was attenuated in the cochlea of the transgenic mice. Thus, we concluded that NRF2 pathway activation protects the cochlea from oxidative damage during aging. Nrf2 activation drugs are expected to be effective in the prevention of AHL.

Free Research Field

酸化ストレスに伴う難聴の予防法の解明

Academic Significance and Societal Importance of the Research Achievements

加齢性難聴は高齢化社会の進展に伴い患者数の増加が懸念されている疾病である。さらに、難聴と認知機能の低下の関連がWHOより報告され、健康長寿社会実現のための加齢性難聴対策の重要性が広く認識されるようになってきた。これまでに加齢性難聴の有効な予防法は解明されていない。本研究では、生体の抗酸化能の中心を担う転写因子Nrf2に着目し、Nrf2の活性化が加齢性難聴の進行を予防することをマウス実験で明らかにした。この結果は、Nrf2が加齢性難聴予防の臨床的ターゲットになることを示唆しており、今後の臨床応用に向けた研究の発展が期待される。