时间标签：数据日期 2026-11-01 · 生成时间 2026-11-01 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/10/31–2026/11/01 ｜ 情报发生日期 2026-11-01
研究问题
The pathogenesis of SAE may be associated with neuroinflammatory responses, synaptic dysfunction, and cell death [ , ]; however, the precise mechanism remains unclear.；However, further investigations are needed to determine whether STING regulates PKM2 during synaptic plasticity‐related energy metabolism in SAE mice.；In this study, we demonstrated that SAE mice had disrupted hippocampal glycolysis, impaired synaptic plasticity, and obvious cognitive dysfunction.
方法
Golgi staining data were compared using nested t ‐test or nested one‐way ANOVA. p < 0.05 was considered statistical significance. 3；As shown in Figure , the mice were randomly divided into four groups: Control + Sham + STING‐shRNA, PKM2 cKO + Sham + STING‐shRNA, Control + CLP + STING‐shRNA, and PKM2 cKO + CLP + STING‐shRNA.；Statistical differences between groups were evaluated using one‐ or two‐way analysis of variance (ANOVA), followed by Tukey's post hoc test with Bonferroni correction to reduce false positives.
核心结论
Furthermore, our results demonstrated that the enhancement of micro‐ER‐phagy activity improved cognitive impairment, alleviated synaptic dysfunction, and increased PKM2 activity in SAE mice.；No significant differences in motor ability were detected among the four groups of mice (Figure ); however, cognitive impairment significantly improved in SAE + STING‐shRNA mice (Figure ).；Subsequently, we found that Sec62 overexpression significantly shortened the half‐life of STING compared to that in vector‐transduced cells, whereas co‐treatment with BafA1 effectively reversed this effect (Figure ).；However, we treated mice with BafA1 to inhibit lysosomal activity and found that the expression levels of Sec62, LC3 II/LC3 I, p62, and STING proteins in the hippocampi of SAE + BafA1 mice were significantly increased (Figure ).
局限
This limitation needs to be addressed in future studies.；Second, direct morphological evidence for lysosomal trafficking of STING will be pursued in future studies. 5 Conclusion In summary, the STING‐mediated inhibition of PKM2 activity triggered defective synaptic plasticity and cognitive…
对本项目的价值
临床前机制证据，需评估物种外推与剂量可行性：营养感知—自噬—蛋白稳态轴决定干预窗口与剂量方案，是组合疗法的时间锚。 ｜ 价值分 3.2/5（★★★☆☆）
全文来源
PubMed PMC JATS 全文（正文 44,986 字符，已过 DOI 逐字 + 题名指纹双重归属校验）
原文题录
- 英文标题：Endoplasmic Reticulum Autophagy Enhancement Alleviates Synaptic Plasticity Dysfunction and Ameliorates Cognitive Impairment in SAE Mice by Relieving STING-Associated Inhibition of PKM2 Activity.
- 期刊与标识：CNS neuroscience & therapeutics · PMID 42954115 · DOI 10.1002/cns.71233
B 级证据分级：B 级（同行评议临床前研究，主要为动物模型）
本文核心结论来自动物模型或体外细胞学，属临床前证据，不能外推至人体。「延长健康寿命」「改善功能」等表述在小鼠中的意义，与人类临床结局之间仍有距离。
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