Evidence mapPaperPMID 39375536Full record

ArticleThe EMBO journal2024

O-GlcNAcylation of circadian clock protein Bmal1 impairs cognitive function in diabetic mice.

Ya Hui, Yuanmei Zhong, Liuyu Kuang, Jingxi Xu, Yuqi Hao, Jingxue Cao, Tianpeng Zheng

Abstract read
In one paragraph

Article in The EMBO journal, 2024. 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

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3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

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4 · The record

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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

7 authors.

Ya Hui *Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Guilin Medical University, 541199, Guilin, Guangxi, P. R. China.
Yuanmei Zhong *Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Guilin Medical University, 541199, Guilin, Guangxi, P. R. China.
Liuyu Kuang *Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Guilin Medical University, 541199, Guilin, Guangxi, P. R. China.
Jingxi Xu *Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Guilin Medical University, 541199, Guilin, Guangxi, P. R. China.
Yuqi HaoDepartment of Endocrinology and Metabolism, The Second Affiliated Hospital of Guilin Medical University, 541199, Guilin, Guangxi, P. R. China.
Jingxue CaoDepartment of Endocrinology and Metabolism, The Second Affiliated Hospital of Guilin Medical University, 541199, Guilin, Guangxi, P. R. China.
Tianpeng ZhengDepartment of Endocrinology and Metabolism, The Second Affiliated Hospital of Guilin Medical University, 541199, Guilin, Guangxi, P. R. China. ZhengTP@glmc.edu.cn.ORCID http://orcid.org/0000-0001-6068-4780

Funding

Graduate Research Program of Guilin Medical University GYYK2022016Innovation Project of Guangxi Graduate Education YCSW2023409Innovation Project of Guangxi Graduate Education YCSW2023424Innovation Project of Guangxi Graduate Education YCSW2024459MOST | National Natural Science Foundation of China (NSFC) 82260171MOST | National Natural Science Foundation of China (NSFC) 82470878natural Science Foundation of Guangxi Province 2015GXNSFBA139119Natural Science Foundation of Guangxi Province of Distinguished Young Scholars 2021GXNSFFA196003Scientific Research and Technology Development Projects of Science and Technology Department of Guangxi Province 1598012-13
6 · The paper itself

Abstract

Neuronal damage in the hippocampus induced by high glucose has been shown to promote the onset and development of cognitive impairment in diabetes, but the underlying molecular mechanism remains unclear. Guided by single-cell RNA sequencing, we here report that high glucose increases O-GlcNAcylation of Bmal1 in hippocampal neurons. This glycosylation promotes the binding of Clock to Bmal1, resulting in the expression of transcription factor Bhlhe41 and its target Dnajb4. Upregulated Dnajb4 in turn leads to ubiquitination and degradation of the mitochondrial Na + /Ca2+ exchanger NCLX, thereby inducing mitochondrial calcium overload that causes neuronal damage and cognitive impairment in mice. Notably, Bhlhe41 downregulation or treatment with a short peptide that specifically blocks O-GlcNAcylation of Bmal1 on Ser424 mitigated these adverse effects in diabetic mouse models. These data highlight the crucial role of O-GlcNAcylation in circadian clock gene expression and may facilitate the design of targeted therapies for diabetes-associated cognitive impairment.

Indexed as

ARNTL Transcription FactorsCognitive DysfunctionDiabetes Mellitus, ExperimentalHippocampusAnimalsBasic Helix-Loop-Helix ProteinsCircadian ClocksCLOCK ProteinsCognitionGlucoseGlycosylationHumansMaleMiceMice, Inbred C57BLNeuronsARNTL Transcription FactorsBasic Helix-Loop-Helix ProteinsBmal1 protein, mouseClock protein, mouseCLOCK ProteinsGlucoseBmal1-Clock ComplexCognitive ImpairmentDiabetesMitochondria Calcium OverloadO-GlcNAcylation

Identifiers

PMID39375536
PMCPMC11574178

What Socratic holds

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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.