Evidence map›Paper›PMID 40366559›Full record

ArticleMolecular neurobiology2025

Melatonin Inhibiting Neuronal Cells Ferroptosis Through Lipid Metabolic Reprogramming.

Haifeng Wang, Fanyong Gong, Wenhui Zhao, Yi Huang, Chenhui Zhou, Jianyong Wang

Abstract read
PubMed Publisher
In one paragraph

Article in Molecular neurobiology, 2025. 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

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

6 authors.

Haifeng Wang *Department of Neurosurgery, Ningbo Key Laboratory of Neurological Diseases and Brain Function, The First Affiliated Hospital of Ningbo University, Ningbo, 315010, Zhejiang Province, China. haifeng_wang@nbdyyy.com.
Fanyong Gong *Department of Neurosurgery, Ningbo Key Laboratory of Neurological Diseases and Brain Function, The First Affiliated Hospital of Ningbo University, Ningbo, 315010, Zhejiang Province, China.
Wenhui ZhaoPsychosomatic Medical Center, The First Affiliated Hospital of Ningbo University, Ningbo, 315010, Zhejiang Province, China. fyyzhaowenhui@nbu.edu.con.
Yi HuangDepartment of Neurosurgery, Ningbo Key Laboratory of Neurological Diseases and Brain Function, The First Affiliated Hospital of Ningbo University, Ningbo, 315010, Zhejiang Province, China.
Chenhui ZhouDepartment of Neurosurgery, Ningbo Key Laboratory of Neurological Diseases and Brain Function, The First Affiliated Hospital of Ningbo University, Ningbo, 315010, Zhejiang Province, China.
Jianyong WangDepartment of Neurosurgery, Ningbo Key Laboratory of Neurological Diseases and Brain Function, The First Affiliated Hospital of Ningbo University, Ningbo, 315010, Zhejiang Province, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

This study aims to identify the underlying mechanism by which melatonin protects neurons. Firstly, the inhibitory effect of melatonin on ferroptosis was verified by treating HT22 cells with melatonin, Erastin, and Ferrostatin-1. Secondly, transcriptomic and metabolomic analyses were performed. Melatonin-related hub genes were identified by differential gene expression analysis, and lipid metabolism-related critical signaling pathways and biological processes (BPs) were determined by gene set enrichment analysis (GSEA). Finally, the expression of hub genes was verified by quantitative real-time PCR (qRT-PCR) or Western Blot (WB), and the involvement of Tribble 3 (Trib3) in the regulation of lipid metabolism and ferroptosis by melatonin was confirmed by Cell Counting Kit 8 (CCK-8) assay, ROS analysis, and WB. Assay results showed that melatonin significantly increased Gpx4 activity, decreased ROS generation, and inhibited ferroptosis in HT22 cells. The hub gene Trib3 was obtained by transcriptomic analysis, and its expression was upregulated with Erastin treatment. Lipid metabolomic analysis suggested that the regulation of lipid metabolism by melatonin was associated with glycerophospholipids. In vitro experiments showed that Trib3 was regulated by the upstream factor Atf4, and the protein levels of Trib3 and Atf4 were significantly increased after Erastin treatment. However, melatonin can reduce the protein levels of Trib3 and Atf4, increase the survival rate of HT-22 cells and the activity of GPX4, and reduce the ROS content. Melatonin inhibits neuronal ferroptosis by affecting the Atf4/Trib3 axis via the modulation of lipid metabolism.

Indexed as

FerroptosisLipid MetabolismMelatoninNeuronsActivating Transcription Factor 4AnimalsCell LineMetabolic ReprogrammingMicePhospholipid Hydroperoxide Glutathione PeroxidaseReactive Oxygen SpeciesSignal TransductionActivating Transcription Factor 4MelatoninPhospholipid Hydroperoxide Glutathione PeroxidaseReactive Oxygen SpeciesAtf4FerroptosisLipid metabolismMelatoninNeuronal cellsTrib3

Identifiers

PMID40366559

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.