Evidence map›Paper›PMID 42263678›Full record

ArticleNeuron2026

Epigenetic control of microglial mitochondrial immunity by KAT7 drives Alzheimer's disease pathogenesis.

Yongqing Liu, Yingzhi Ye, Minghua Fan, Henry Yi Cheng, Shuying Sun, Zhaozhu Qiu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Yongqing LiuDepartment of Physiology, Pharmacology and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Yingzhi YeDepartment of Physiology, Pharmacology and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Minghua FanSolomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Henry Yi ChengDepartment of Physiology, Pharmacology and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Shuying SunDepartment of Physiology, Pharmacology and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Brain Science Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Zhaozhu QiuDepartment of Physiology, Pharmacology and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: zhaozhu@jhmi.edu.

Funding

Molecular Identity and Physiological Function of Novel Chloride ChannelsR35GM124824 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI Zhaozhu Qiu · 2017 to 2026
$4.8M
Validation of a new large-pore channel as a novel target for neuropathic painRF1NS134549 · NINDS · JOHNS HOPKINS UNIVERSITY · PI Yun Guan, Zhaozhu Qiu · 2023 to 2026
$3.4M
Cell Swelling-Activated Chloride Channel in Ischemic StrokeR01NS118014 · NINDS · JOHNS HOPKINS UNIVERSITY · PI QIU, ZHAOZHU · 2020 to 2024
$2.6M
NIGMS NIH HHS R35 GM124824NINDS NIH HHS R01 NS118014NINDS NIH HHS RF1 NS134549
6 · The paper itself

Abstract

Mitochondrial DNA (mtDNA)-driven innate immune signaling sustains chronic neuroinflammation in neurological diseases such as Alzheimer's disease (AD), yet how this pathway is regulated in microglia remains poorly understood. Here, we identify the histone acetyltransferase KAT7 (HBO1) as a central epigenetic regulator that links chromatin remodeling to mitochondrial immune activation. KAT7 and its histone mark H3K14ac are elevated in microglia from 5×FAD mice and human AD brains. Integrative transcriptomic and epigenomic analyses reveal that KAT7 activates transcription of cytidine/uridine monophosphate kinase 2 (Cmpk2), a mitochondrial kinase essential for mtDNA synthesis. Loss of KAT7 reduces Cmpk2 expression, impairs mtDNA replication and release, and consequently suppresses cyclic guanosine monophosphate-AMP synthase (cGAS)-stimulator of interferon genes (STING) and NLRP3 signaling. Importantly, both microglia-specific deletion and pharmacological inhibition of KAT7 mitigate cytosolic mtDNA-induced neuroinflammation, decrease β-amyloid burden, restore synaptic plasticity, and improve cognitive function in 5×FAD mice. Together, these findings uncover an epigenetic-mitochondrial axis sustaining microglial pathogenicity and establish KAT7 as a potential therapeutic target for AD.

Indexed as

Alzheimer’s diseasecGAS-STINGCMPK2KAT7microgliamitochondrial DNAneuroinflammation

Identifiers

PMID42263678
PMCPMC13256259

What OpenQuestion holds

Textmetadata
LicenceTDM
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.