Evidence map›Paper›PMID 33925146›Full record

ArticleInternational journal of molecular sciences2021

The Neuroprotective Effects of GPR4 Inhibition through the Attenuation of Caspase Mediated Apoptotic Cell Death in an MPTP Induced Mouse Model of Parkinson's Disease.

Md Ezazul Haque, Shofiul Azam, Mahbuba Akther, Duk-Yeon Cho, In-Su Kim, Dong-Kug Choi

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.5field-weighted citation impact, top 9% 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

14 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Neuroprotection: Rescue from Neuronal Death in the Brain 2.0.International journal of molecular sciences · 2023
    Article
  12. Article
  13. Physiological relevance of proton-activated GPCRs.Pflugers Archiv : European journal of physiology · 2022
    Review
  14. 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

6 authors at 1 institution in 1 country.

Md Ezazul HaqueDepartment of Applied Life Science, Graduate School, BK21 Program, Konkuk University, Chungju 27478, Korea.ORCID 0000-0002-5625-3547
Shofiul AzamDepartment of Applied Life Science, Graduate School, BK21 Program, Konkuk University, Chungju 27478, Korea.ORCID 0000-0003-4707-3488
Mahbuba AktherDepartment of Applied Life Science, Graduate School, BK21 Program, Konkuk University, Chungju 27478, Korea.
Duk-Yeon ChoDepartment of Applied Life Science, Graduate School, BK21 Program, Konkuk University, Chungju 27478, Korea.
In-Su KimDepartment of Biotechnology, College of Biomedical and Health Science, and Research Institute of Inflammatory Disease (RID), Konkuk University, Chungju 27478, Korea.ORCID 0000-0001-5755-8433
Dong-Kug ChoiDepartment of Applied Life Science, Graduate School, BK21 Program, Konkuk University, Chungju 27478, Korea.ORCID 0000-0001-7041-1524
Konkuk University · KR

Funding

National Research Foundation of Korea (NRF) (NRF-2018R1C1B6005129
6 · The paper itself

Abstract

The proton-activated G protein-coupled receptor (GPCR) 4 (GPR4) is constitutively active at physiological pH, and GPR4 knockout protected dopaminergic neurons from caspase-dependent mitochondria-associated apoptosis. This study explored the role of GPR4 in a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated mouse model of Parkinson's disease (PD). In mice, subchronic MPTP administration causes oxidative stress-induced apoptosis in the dopaminergic neurons of the substantia nigra pars compacta (SNpc), resulting in motor deficits. NE52-QQ57, a selective GPR4 antagonist, reduced dopaminergic neuronal loss in MPTP-treated mice, improving motor and memory functions. MPTP and NE52-QQ57 co-treatment in mice significantly decreased pro-apoptotic marker Bax protein levels and increased anti-apoptotic marker Bcl-2 protein levels in the SNpc and striatum. MPTP-induced caspase 3 activation and poly (ADP-ribose) polymerase (PARP) cleavage significantly decreased in the SNpc and striatum of mice co-treated with NE52-QQ57. MPTP and NE52-QQ57 co-treatment significantly increased tyrosine hydroxylase (TH)-positive cell numbers in the SNpc and striatum compared with MPTP alone. NE52-QQ57 and MPTP co-treatment improved rotarod and pole test-assessed motor performance and improved Y-maze test-assessed spatial memory. Our findings suggest GPR4 may represent a potential therapeutic target for PD, and GPR4 activation is involved in caspase-mediated neuronal apoptosis in the SNpc and striatum of MPTP-treated mice.

Indexed as

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridineAnimalsApoptosisBrainCaspase 3CaspasesCorpus StriatumDopamineDopaminergic NeuronsMaleMiceMice, Inbred C57BLNeuroprotective AgentsParkinson DiseasePars CompactaProto-Oncogene Proteins c-bcl-21-Methyl-4-phenyl-1,2,3,6-tetrahydropyridineBcl2 protein, mouseCaspase 3CaspasesDopamineGPR4 protein, mouseNeuroprotective AgentsProto-Oncogene Proteins c-bcl-2Receptors, G-Protein-CoupledTyrosine 3-Monooxygenaseapoptosiscaspase 3GPR4 receptorMPTPneurodegenerationParkinson’s diseasePARP

Identifiers

PMID33925146
PMCPMC8125349
OpenAlexW3147866090

What OpenQuestion 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 OpenQuestion graph.