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Updated: Nov 30, 2025
A Thrombotic Stroke Model Based On Transient Cerebral Hypoxia-ischemia
Published on: August 18, 2015
YTHDC1 mitigates ischemic stroke by promoting Akt phosphorylation through destabilizing PTEN mRNA
Zhaolong Zhang1, Qiuhan Wang1, Xiaolong Zhao1
1Department of Interventional Radiology, the Affiliated Hospital of Qingdao University, Jiangsu Road 16, Qingdao, 266000, Shandong, China.
Insights
YTHDC1 regulates neuronal survival after ischemic stroke. Modulating this m6A reader offers a potential therapeutic strategy for stroke, as YTHDC1 protects against brain injury.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- YTH Domain Containing 1 (YTHDC1) is an m6A reader crucial for oocyte development and tumor progression.
- The function of YTHDC1 in neuronal survival and its role in ischemic stroke remain uncharacterized.
Purpose of the Study:
- To investigate the role of YTHDC1 in neuronal survival following ischemic stroke.
- To elucidate the underlying molecular mechanisms of YTHDC1 in the context of ischemic brain injury.
Main Methods:
- Investigated YTHDC1 expression in the early phase of ischemic stroke.
- Utilized knockdown and overexpression models in rats to assess the impact of YTHDC1 on ischemic brain injury.
- Examined the effect of YTHDC1 on PTEN mRNA degradation and Akt phosphorylation.
Main Results:
- YTHDC1 expression was upregulated in the early stages of ischemic stroke.
- YTHDC1 knockdown worsened ischemic brain injury, while its overexpression conferred protection.
- YTHDC1 was found to promote PTEN mRNA degradation, leading to increased Akt phosphorylation and enhanced neuronal survival post-ischemia.
Conclusions:
- YTHDC1 acts as a novel regulator of neuronal survival in the context of ischemic stroke.
- Targeting the m6A reader YTHDC1 presents a potential therapeutic avenue for treating ischemic stroke.
Abstract:
YTH Domain Containing 1 (YTHDC1) is one of the m6A readers that is essential for oocyte development and tumor progression. The role of YTHDC1 in neuronal survival and ischemic stroke is unknown. Here, we found that YTHDC1 was unregulated in the early phase of ischemic stroke. Knockdown of YTHDC1 exacerbated ischemic brain injury and overexpression of YTHDC1 protected rats against brain injury. Mechanistically, YTHDC1 promoted PTEN mRNA degradation to increase Akt phosphorylation, thus facilitating neuronal survival in particular after ischemia. These data identify YTHDC1 as a novel regulator of neuronal survival and modulating m6A reader YTHDC1 may provide a potential therapeutic target for ischemic stroke.
