Evidence map›Paper›PMID 31383850›Full record

ArticleCell death & disease2019

miR-425 deficiency promotes necroptosis and dopaminergic neurodegeneration in Parkinson's disease.

Yong-Bo Hu, Yong-Fang Zhang, Hao Wang, Ru-Jing Ren, Hai-Lun Cui, Wan-Ying Huang, Qi Cheng, Hong-Zhuan Chen, Gang Wang

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

67 citing papers in PubMed, 113 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. MicroRNAs in neurodegenerative diseases: from molecular mechanisms to clinical biomarkers, detection methods and therapeutic strategies-advances and challenges.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
    Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. RIPK1: A Promising Target for Intervention Neuroinflammation.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025
    Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Review
  19. Review
  20. The Role of Estrogen in Brain MicroRNAs Regulation.Advanced pharmaceutical bulletin · 2024
    Review

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

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

9 authors at 1 institution in 1 country.

Yong-Bo HuDepartment of Neurology & Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China.
Yong-Fang ZhangDepartment of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China.
Hao WangDepartment of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China. angela_wanghao@hotmail.com.
Ru-Jing RenDepartment of Neurology & Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China.
Hai-Lun CuiDepartment of Neurology & Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China.
Wan-Ying HuangDepartment of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China.
Qi ChengSchool of Public health Shanghai Jiao Tong university, 200025, Shanghai, China.
Hong-Zhuan ChenDepartment of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China.
Gang WangDepartment of Neurology & Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China. wgneuron@hotmail.com.ORCID http://orcid.org/0000-0001-6500-5863
Shanghai Jiao Tong University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A major hallmark of Parkinson's disease (PD) is the degeneration of dopaminergic neurons in the substantia nigra, and the causative mechanism is thought to be the activation of programmed neuronal death. Necroptosis is a regulated process of cell death triggered by RIPK1. Although the pathophysiology of PD has been studied extensively, the cellular mechanism underlying dopaminergic neuron death remains unclear. In this study, we detected a specific miRNA, miR-425, in response to MPTP toxicity and dopaminergic degeneration. In MPTP-treated mice, we observed necroptosis activation and miR-425 deficiency in the substantia nigra, which is correlated with dopaminergic neuron loss. This miRNA targeted RIPK1 transcripts and promoted the phosphorylation of MLKL and necroptosis. Similarly, in the brains of PD patients, miR-425 deficiency and necroptosis activation were also confirmed in dopaminergic neuron. Furthermore, we found that genetic knockdown of miR-425 aggravated MPTP-induced motor deficits and dopaminergic neurodegeneration via early upregulation of necroptotic genes. Intracerebral miR-425 mimics (AgomiR-425) treatment attenuated necroptosis activation and dopaminergic neuron loss, and improved locomotor behaviors. In conclusion, our study suggests that miR-425 deficiency triggers necroptosis of dopaminergic neurons, and targeting miR-425 in MPTP-treated mice restored dysfunctional dopaminergic neurodegeneration and ameliorated behavioral deficits. These findings identify brain delivery of miR-425 as a potential therapeutic approach for the treatment of PD.

Indexed as

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridineAnimalsAntagomirsDisease Models, AnimalDopamineDopaminergic NeuronsGene Knockdown TechniquesHumansLocomotionMaleMiceMice, Inbred C57BLMice, TransgenicMicroRNAsNecroptosisNerve Degeneration1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridineAntagomirsDopamineMicroRNAsMIRN425 microRNA, humanMIRN425 microRNA, mouseNeurotoxins

Identifiers

PMID31383850
PMCPMC6683159
OpenAlexW2965446050

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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 OpenQuestion graph.