Evidence mapPaperPMID 40544260Full record

ArticleJournal of neuroinflammation2025

Targeting the RAGE-RIPK1 binding site attenuates diabetes-associated cognitive deficits.

Lin Gao, Shidi Wu, Bin Hu, Qiuyu Zhang, Yifei Wu, Hui Li, Ye Qian, Chengyu Huang, Xiangru Wen, Hui Li and 4 more

Abstract read
In one paragraph

Article in Journal of neuroinflammation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Lin Gao *The Graduate School, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
Shidi Wu *The Graduate School, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
Bin Hu *Jiangsu Key Laboratory of Brain Disease and Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
Qiuyu ZhangThe Graduate School, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
Yifei WuThe Graduate School, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
Hui LiThe Graduate School, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
Ye QianThe Graduate School, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
Chengyu HuangThe Graduate School, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
Xiangru WenDepartment of Genetics, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
Hui LiJiangsu Key Laboratory of Brain Disease and Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
Aifang ChengDepartment of Biomedical Sciences, Faculty of Health Sciences, University of Macau, SAR, Taipa, 999078, Macao, China.
Yuanjian SongDepartment of Genetics, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China. yjsong@xzhmu.edu.cn.
Changjiang YingJiangsu Engineering Center for Precision Diagnosis and Treatment Research of Polygenic Diseases, Xuzhou, 221000, Jiangsu, China. ycj321651@163.com.
Xiaoyan ZhouDepartment of Genetics, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China. zhouxiaoyan0201@xzhmu.edu.cn.

Funding

National Natural Science Foundation of China 82271205Natural Science Foundation of Jiangsu Province BK20221216
6 · The paper itself

Abstract

Microglial activation can cause neuroinflammation and the consequent neurological impairments play prominent roles in diabetes-associated cognitive deficits. Receptor-interacting protein kinase 1 (RIPK1) phosphorylation is involved in this deleterious microglial activation, but the exact molecular mechanisms are not clear. Here, RIPK1 expression was increased in diabetic patients with cognitive impairment. Furthermore, in diabetic mice, RIPK1 death domain directly binds to C-terminal of the receptor for advanced glycation end products (ctRAGE) could regulate RIPK1 phosphorylation in microglia. This RAGE-RIPK1 complex activates inflammatory signaling, resulting in cascades that ultimately promote cognitive impairment in diabetic mice. An engineered brain-targeting RIPK1 peptide blocked binding of RIPK1 to RAGE, which inhibited RIPK1 phosphorylation, decreased neuroinflammation, improved neuronal morphology and function, and prevented diabetes-associated cognitive deficits in mice. This study uncovers a previously unknown mechanism of neuroinflammation and suggests a novel therapeutic avenue for treating cognitive deficits induced by hyperglycemia.

Indexed as

Cognitive DysfunctionDiabetes Mellitus, ExperimentalReceptor for Advanced Glycation End ProductsReceptor-Interacting Protein Serine-Threonine KinasesAnimalsBinding SitesHumansMaleMiceMice, Inbred C57BLMicrogliaAger protein, mouseReceptor for Advanced Glycation End ProductsReceptor-Interacting Protein Serine-Threonine KinasesRIPK1 protein, humanRipk1 protein, mouseDiabetes-associated cognitive deficitsNeuroinflammationReceptor-interacting protein kinase 1RIPK1 peptideThe receptor for advanced glycation end products

Identifiers

PMID40544260
PMCPMC12182694

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.