Evidence map›Paper›PMID 30668640›Full record

ArticleBrain : a journal of neurology2019

Inhibition of EHMT1/2 rescues synaptic and cognitive functions for Alzheimer's disease.

Yan Zheng, Aiyi Liu, Zi-Jun Wang, Qing Cao, Wei Wang, Lin Lin, Kaijie Ma, Freddy Zhang, Jing Wei, Emmanuel Matas and 4 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain : a journal of neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
105citing papers in PubMed, 1 pooled it
6.4field-weighted citation impact, top 2% of its field
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

105 citing papers in PubMed, 1 synthesis or guideline pooled it, 173 citations in OpenAlex.

  1. Pooled it
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  5. Article
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  7. Article
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  13. Epigenomic profile of GBA1 in Parkinson's disease.Parkinsonism & related disorders · 2025
    Article
  14. Review
  15. Article
  16. Article
  17. Cell type-specific master metabolic regulators of Alzheimer's disease.bioRxiv : the preprint server for biology · 2025
    Article
  18. Article
  19. Article
  20. Review

45 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 2 countries.

Yan ZhengDepartment of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
Aiyi LiuDepartment of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
Zi-Jun WangDepartment of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
Qing CaoDepartment of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
Wei WangDepartment of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
Lin LinDepartment of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
Kaijie MaDepartment of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
Freddy ZhangDepartment of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
Jing WeiDepartment of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
Emmanuel MatasDepartment of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
Jia ChengDepartment of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
Guo-Jun ChenDepartment of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, P.R.China.
Xiaomin WangDepartment of Physiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, P.R.China.
Zhen YanDepartment of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
University at Buffalo, State University of New York · USCapital Medical University · CNVA Western New York Healthcare System · USChongqing Medical University · CNFirst Affiliated Hospital of Chongqing Medical University · CN

Funding

Targeting Histone K4 Methylation for Treatment of Alzheimer's Disease and Related DementiaR01AG064656 · NIA · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI YAN, ZHEN · 2019 to 2023
$2.5M
A Novel Epigenetic Mechanism for Alzheimer's DiseaseR01AG056060 · NIA · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI YAN, ZHEN · 2017 to 2021
$2.2M
BLRD VA I01 BX001633NIA NIH HHS R01 AG056060NIA NIH HHS R01 AG064656
6 · The paper itself

Abstract

Epigenetic dysregulation, which leads to the alteration of gene expression in the brain, is suggested as one of the key pathophysiological bases of ageing and neurodegeneration. Here we found that, in the late-stage familial Alzheimer's disease (FAD) mouse model, repressive histone H3 dimethylation at lysine 9 (H3K9me2) and euchromatic histone methyltransferases EHMT1 and EHMT2 were significantly elevated in the prefrontal cortex, a key cognitive region affected in Alzheimer's disease. Elevated levels of H3K9me2 were also detected in the prefrontal cortex region of post-mortem tissues from human patients with Alzheimer's disease. Concomitantly, H3K9me2 at glutamate receptors was increased in prefrontal cortex of aged FAD mice, which was linked to the diminished transcription, expression and function of AMPA and NMDA receptors. Treatment of FAD mice with specific EHMT1/2 inhibitors reversed histone hyper-methylation and led to the recovery of glutamate receptor expression and excitatory synaptic function in prefrontal cortex and hippocampus. Chromatin immunoprecipitation-sequencing (ChIP-seq) data indicated that FAD mice exhibited genome-wide increase of H3K9me2 enrichment at genes involved in neuronal signalling (including glutamate receptors), which was reversed by EHMT1/2 inhibition. Moreover, the impaired recognition memory, working memory, and spatial memory in aged FAD mice were rescued by the treatment with EHMT1/2 inhibitors. These results suggest that disrupted epigenetic regulation of glutamate receptor transcription underlies the synaptic and cognitive deficits in Alzheimer's disease, and targeting histone methylation enzymes may represent a novel therapeutic strategy for this prevalent neurodegenerative disorder.

Indexed as

Alzheimer DiseaseAnimalsChromosome DeletionCognitionCognition DisordersCognitive DysfunctionDisease Models, AnimalDNA MethylationEpigenesis, GeneticHippocampusHistocompatibility AntigensHistone-Lysine N-MethyltransferaseHistonesHumansLysineMemory DisordersEHMT1 protein, humanEHMT2 protein, humanHistocompatibility AntigensHistone-Lysine N-MethyltransferaseHistonesLysineAlzheimer’s diseaseepigeneticsglutamate receptorhistone methylationmemory

Identifiers

PMID30668640
PMCPMC6391616
OpenAlexW2914500235

What OpenQuestion holds

Textmetadata
Read underepoch 390

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 OpenQuestion graph.