2. Academic Validation
  3. SIRT1 induces FOXO1/autophagy/NCOA4-induced ferroptosis and accelerates the progression of cerebral infarction by inhibiting the E2F1/NOTCH-1/YAP signaling pathway

SIRT1 induces FOXO1/autophagy/NCOA4-induced ferroptosis and accelerates the progression of cerebral infarction by inhibiting the E2F1/NOTCH-1/YAP signaling pathway

  • Sci Rep. 2026 Mar 17;16(1):13946. doi: 10.1038/s41598-026-44355-1.
Gang Wang # 1,  Shuyu Ma # 2,  Linjie Qi 3,  Jianhua Wang 4,  Ying Zhou 5,  LiJiao Jia 1,  Guang Hao 1,  Zuopeng Li 6
Affiliations

Affiliations

  • 1 Department of Neurology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, 075000, China.
  • 2 Department of School of Clinical Medicine, The First Clinical Medical College of Shanxi Medical University, Taiyuan, 030000, China.
  • 3 Department of The First Affiliated Hospital of Hebei North University, Zhangjiakou, 075000, China.
  • 4 Department of Zhangjiakou Hospital of Traditional Chinese Medicine, Zhangjiakou, 075000, China.
  • 5 Department of ICU, The First Affiliated Hospital of Hebei North University, Zhangjiakou, 075000, China.
  • 6 Department of Neurology, The First Clinical Medical College of Shanxi Medical University, No. 85, Jiefang South Road, Yingze District, Taiyuan, 030000, Shanxi, China. [email protected].
  • # Contributed equally.
PMID: 41844756 DOI: 10.1038/s41598-026-44355-1
Abstract

To access the effect of SIRT1 in cerebral infarction and to explore its mechanism of Ferroptosis. Bioinformatic Analysis was used to discover the associations between Ferroptosis-Related Genes and Cerebral Infarction.Rat cerebral infarction model was induced by transient middle cerebral artery occlusion followed by reperfusion.In vitro experiments, astrocytes were subjected to different stimuli.HE staining was used to observe the area of cerebral infarction in rat models.The expression of Autophagy proteins and ferroptosis-related proteins in vivo and vitro experiments was accessed by using Western blot analysis and immunofluorescence, and Apoptosis was detected by flow Apoptosis assay. Detection of MDA, Fe2+, and SOD expression using ELISA. SIRT1 was upregulated in cerebral infarction model and the area of cerebral infarction increased when SIRT1 was actived, while it decreased in Notch-1 over oxpressing.In cell experiments, SIRT1 inhibited the expression of nuclear E2F1,Notch-1,nuclear YAP and up-regulated the expression of FOX1,Beclin-2, p62 and NCOA4,which led to the Apoptosis of astrocytes. Furthermore, activation of SIRT1 suppresses the expression of MDA and Fe2+ while promoting the expression of SOD. SIRT1 ultimately accelerated cerebral infarction progression by inhibiting the E2F1/Notch-1/YAP signaling pathway and thereby inducing FOXO1/Autophagy/NCOA4-induced Ferroptosis.

Keywords

Cerebral infarction; E2F1/NOTCH-1/YAP; FOXO1/autophagy/NCOA4; Ferroptosis; SIRT1.

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