OAC1 improves mitofusin 2 expression to alleviate neuronal injury following experimental ischemic stroke

• 발행기관: 대한생리학회-대한약리학회
• 저자명: Yuanyuan Wang Kechun Chen Bingtian Xu Haitao Wang Honghao Wang Tianming Lü
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제29권 제6호, 741~753쪽, 전체 13쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2025.11.30

국문 초록

Recent research indicates that mitofusin 2 (MFN2) plays a pivotal role in the neuroprotective effects achieved by silencing nuclear receptor subfamily 6 group A member 1 (NR6A1) during cerebral ischemia. While NR6A1 is known to inhibit octamer-binding transcription factor 4 (OCT4), the regulatory relationship between OCT4 and MFN2 remains unknown. This study explores the neuroprotective effects of OCT4-activating compound 1 (OAC1), an OCT4 activator, against cerebral ischemia/reperfusion injuries and its underlying mechanism. In a murine stroke model, administration of OAC1 (3 mg/kg) significantly reduced brain infarction of mice and loss of MFN2. Notably, OAC1 treatment mitigated neuronal injury induced by oxygen–glucose deprivation/reoxygenation (OGD/R) in a dose-dependent manner. Additionally, OAC1 treatment also alleviated dysfunction of mitochondria and endoplasmic reticulum stress. Moreover, OAC1 application preserved both OCT4 and MFN2 expression following OGD/R, and MFN2 facilitate protective function of OAC1 against neuronal damage induced by OGD/R. Our results demonstrate that OAC1 can alleviate neuronal damage in cerebral ischemia by activating the OCT4/MFN2. These findings offer novel insights into MFN2 regulation and highlight OCT4’s potential as a therapeutic target for cerebral ischemia.

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키워드

Brain ischemia Mitofusin 2 Neuronal injury OAC1 Octamer-binding transcription factor 4