Evidence mapPaperPMID 42041604Full record

ArticleCells2026

Metformin Alleviates Cadmium-Induced Autophagic Flux Impairment-Dependent Apoptosis by Activating AMPK in Neuronal Cells.

Wen Wu, Xiaoling Chen, Tong Ji, Qianyun Yu, Long Hou, Zhihan Zhou, Baoming Gong, Ming Xu, Wei Gao, Shile Huang and 1 more

Abstract read
In one paragraph

Article in Cells, 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

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

11 authors.

Wen WuJiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.
Xiaoling ChenJiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.
Tong JiJiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.
Qianyun YuJiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.
Long HouJiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.
Zhihan ZhouJiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.
Baoming GongJiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.
Ming XuJiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.
Wei GaoJiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.
Shile HuangDepartment of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USA.ORCID 0000-0002-3239-1072
Long ChenJiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.ORCID 0000-0002-2050-8050

Funding

American Cancer Society RSG-08-135-01-CNENational Natural Science Foundation of China 81873781, 81271416Natural Science Research Project of Anhui Educational Committee 2022AH051214NCI NIH HHS R01 CA115414NIH HHS CA115414Project for the Priority Academic Program Development of Jiangsu Higher Education Institutions of China PAPD-14KJB180010
6 · The paper itself

Abstract

Cadmium (Cd), a common environmental and occupational toxicant, is an important risk factor for neurodegenerative diseases. Metformin has been found to have neuroprotective effect, in addition to antidiabetic function. Our recent studies have identified that metformin ameliorates Cd neurotoxicity via blocking ROS-dependent PP5/AMPK-JNK signaling pathway. Here we further show that metformin protected PC12 cells and primary neurons from Cd-poisoning by mitigating Cd-induced increases in ATG5/LC3-II/p62 levels and autophagosomes. Knockdown of ATG5 dramatically potentiated the inhibitory effects of metformin on Cd-induced LC3-II, cleavage of caspase-3, accumulation of autophagosomes and apoptosis in PC12 cells. Addition of chloroquine (CQ) strengthened the basic and Cd-elevated ATG5/LC3-II/p62 levels, autophagosome accumulation and cell apoptosis, whereas metformin powerfully blocked the events, implying a metformin-promoted autophagic flux-dependent mechanism involved. Further research revealed that metformin prevented Cd-induced autophagic flux impairment and cell apoptosis, which was attributed to restraining Cd inactivation of AMPK. This is supported by the findings that activation of AMPK with AICAR or ectopic expression of constitutively active AMPKα (AMPKα-ca) reinforced the inhibitory effects of metformin on Cd-evoked ATG5/LC3-II/p62/autophagosomes and apoptosis in PC12 cells and/or primary neurons. Taken together, the results indicate that metformin protects neuronal cells from Cd-induced autophagic flux impairment-dependent apoptosis by activating AMPK. Our studies highlight that metformin has a great potential for prevention of Cd toxicity related to neurodegenerative diseases.

Indexed as

AMP-Activated Protein KinasesApoptosisAutophagyCadmiumMetforminNeuronsAnimalsAutophagosomesAutophagy-Related Protein 5Enzyme ActivationPC12 CellsRatsSignal TransductionAMP-Activated Protein KinasesAutophagy-Related Protein 5CadmiumMetforminAMPKATG5autophagic fluxcadmiummetforminneuronal cells

Identifiers

PMID42041604
PMCPMC13115256

What Socratic holds

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LicenceCC BY
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Registered trials

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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.