Evidence map›Paper›PMID 38644791›Full record

ArticleClinical and translational medicine2024

ACOD1, rather than itaconate, facilitates p62-mediated activation of Nrf2 in microglia post spinal cord contusion.

Zhanyang Qian, Mingjie Xia, Tianyu Zhao, You Li, Guangshen Li, Yanan Zhang, Haijun Li, Lei Yang

Open access · goldAbstract read
In one paragraph

Article in Clinical and translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
8.5field-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

18 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Review
  3. Itaconate and its derivatives in human health and diseases.Signal transduction and targeted therapy · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
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

8 authors at 3 institutions in 2 countries.

Zhanyang QianDepartment of Orthopedics, Taizhou School of Clinical Medicine, Taizhou People's Hospital of Nanjing Medical University, Nanjing Medical University, Taizhou, China.ORCID 0000-0002-6431-9008
Mingjie XiaDepartment of Spine Surgery, Nantong First People's Hospital, The Second Affiliated Hospital of Nantong University, Nantong, China.
Tianyu ZhaoDepartment of Orthopedics, Taizhou School of Clinical Medicine, Taizhou People's Hospital of Nanjing Medical University, Nanjing Medical University, Taizhou, China.
You LiDepartment of Trauma and Reconstructive Surgery, RWTH Aachen University Hospital, Aachen, Germany.
Guangshen LiDepartment of Orthopedics, Taizhou School of Clinical Medicine, Taizhou People's Hospital of Nanjing Medical University, Nanjing Medical University, Taizhou, China.
Yanan ZhangDepartment of Orthopedics, Taizhou School of Clinical Medicine, Taizhou People's Hospital of Nanjing Medical University, Nanjing Medical University, Taizhou, China.
Haijun LiDepartment of Orthopedics, Taizhou School of Clinical Medicine, Taizhou People's Hospital of Nanjing Medical University, Nanjing Medical University, Taizhou, China.ORCID 0009-0000-6649-7847
Lei YangDepartment of Orthopedics, Taizhou School of Clinical Medicine, Taizhou People's Hospital of Nanjing Medical University, Nanjing Medical University, Taizhou, China.ORCID 0000-0001-5677-9955
Nantong University · CNDalian Medical University · CNUniversitätsklinikum Aachen · DE

Funding

Basic Research Program of Jiangsu Province BK20221298China Postdoctoral Science Foundation 2022M721680Traditional Chinese Medicine Technology Development Project of Taizhou City TZ202208
6 · The paper itself

Abstract

backgroundSpinal cord injury (SCI)-induced neuroinflammation and oxidative stress (OS) are crucial events causing neurological dysfunction. Aconitate decarboxylase 1 (ACOD1) and its metabolite itaconate (Ita) inhibit inflammation and OS by promoting alkylation of Keap1 to induce Nrf2 expression; however, it is unclear whether there is another pathway regulating their effects in inflammation-activated microglia after SCI.

methodsAdult male C57BL/6 ACOD1

resultsBoth in vitro and in vivo, microglia with transcriptional blockage of ACOD1 exhibited more severe levels of neuroinflammation and OS, in which the expression of p62/Keap1/Nrf2 was down-regulated. Furthermore, silencing ACOD1 exacerbated neurological dysfunction in SCI mice. Administration of exogenous Ita or 4-octyl itaconate reduced p62 phosphorylation. Besides, ACOD1 was capable of interacting with phosphorylated p62 to enhance Nrf2 activation, which in turn further promoted transcription of ACOD1.

conclusionsHere, we identified an unreported ACOD1-p62-Nrf2-ACOD1 feedback loop exerting anti-inflammatory and anti-OS in inflammatory microglia, and demonstrated the neuroprotective role of ACOD1 after SCI, which was different from that of endogenous and exogenous Ita. The present study extends the functions of ACOD1 and uncovers marked property differences between endogenous and exogenous Ita. KEY POINTS: ACOD1 attenuated neuroinflammation and oxidative stress after spinal cord injury. ACOD1, not itaconate, interacted with p-p62 to facilitate Nrf2 expression and nuclear translocation. Nrf2 was capable of promoting ACOD1 transcription in microglia.

Indexed as

Carboxy-LyasesHydro-LyasesMicrogliaNF-E2-Related Factor 2Spinal Cord InjuriesSuccinatesAnimalsDisease Models, AnimalMaleMiceMice, Inbred C57BLSequestosome-1 ProteinAcod1 protein, mouseCarboxy-LyasesHydro-Lyasesitaconic acidNfe2l2 protein, mouseNF-E2-Related Factor 2Sequestosome-1 ProteinSqstm1 protein, mouseSuccinatesaconitate decarboxylase 1itaconateneuroinflammationNrf2p62spinal cord injury

Identifiers

PMID38644791
PMCPMC11033726
OpenAlexW4395004886

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.