Evidence map›Paper›PMID 42398271›Full record

ArticleRedox biology2026

Inhibiting 15-PGDH restores redox homeostasis and confers neuroprotection in Parkinson's disease.

Young-Kwang Kim, Yun Jae Cha, Se Eun Park, Hee Kyung Kim, Chaesun Kwon, Geonmo Kim, Yoonah R Oh, Edwin Vázquez-Rosa, Ujjwal Dahiya, Helen Moinova and 19 more

Abstract read
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In one paragraph

Article in Redox biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Redefining breast cancer: therapeutic opportunities in HER2-low and emerging molecular subtypes.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
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

29 authors.

Young-Kwang KimCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea; Laboratory of Neurodegenerative Diseases, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
Yun Jae ChaCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
Se Eun ParkCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea; Laboratory of Neurodegenerative Diseases, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
Hee Kyung KimCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea; Laboratory of Neurodegenerative Diseases, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
Chaesun KwonCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea; Laboratory of Neurodegenerative Diseases, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
Geonmo KimCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea; Laboratory of Neurodegenerative Diseases, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
Yoonah R OhCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea; Laboratory of Neurodegenerative Diseases, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
Edwin Vázquez-RosaDepartment of Psychiatry, Case Western Reserve University, Cleveland, OH, USA; Geriatric Psychiatry, GRECC, Louis Stokes VA Medical Center, Cleveland, OH, USA; Institute for Transformative Molecular Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Ujjwal DahiyaCase Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
Helen MoinovaDepartment of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Yeojung KohDepartment of Psychiatry, Case Western Reserve University, Cleveland, OH, USA; Geriatric Psychiatry, GRECC, Louis Stokes VA Medical Center, Cleveland, OH, USA; Institute for Transformative Molecular Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH, USA; Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
Farrah GaoDepartment of Genetics and Genome Sciences School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Sunil Jamuna TripathiDepartment of Physiology, Pharmacology and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Suwarna ChakrabortyDepartment of Physiology, Pharmacology and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Dong-Gyu JoSchool of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
Minseo WooGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
Hyejin ParkGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
Seung-Jae MyungDigestive Diseases Research Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; Edis Biotech, Songpa-gu, Seoul, Republic of Korea.
Jiwon CheonDepartment of Pharmacology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
Yunjong LeeDepartment of Pharmacology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
Xin QiDepartment of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Bindu D PaulDepartment of Physiology, Pharmacology and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Stephen FinkCase Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
Lakshmi KasturiCase Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
James LutterbaughCase Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
Sanford D MarkowitzCase Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA; Department of Medicine, Case Western Reserve University, Cleveland, OH, USA; Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, OH, USA. Electronic address: sxm10@case.edu.
Andrew A PieperDepartment of Psychiatry, Case Western Reserve University, Cleveland, OH, USA; Geriatric Psychiatry, GRECC, Louis Stokes VA Medical Center, Cleveland, OH, USA; Institute for Transformative Molecular Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH, USA; Department of Pathology, Case Western Reserve University, Cleveland, OH, USA; Brain Health Medicines Center, Harrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Department of Neurosciences, Case Western Reserve University, Cleveland, OH, USA. Electronic address: andrew.pieper@case.edu.
Yun Pyo KangCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea. Electronic address: yunpyo.kang@snu.ac.kr.
Min-Kyoo ShinCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea; Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, Republic of Korea; Innovative Pharmaceutical Sciences Program, College of Transdisciplinary Innovations, Seoul National University, Seoul, Republic of Korea; Laboratory of Neurodegenerative Diseases, College of Pharmacy, Seoul National University, Seoul, Republic of Korea. Electronic address: minkyooshin@snu.ac.kr.

Funding

Chemical, Structural and Cell-Signaling Interrogation of 15-Prostanglandin Dehydrogenase in Tissue Repair and RegenerationRM1GM142002 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI MARKOWITZ, SANFORD D., PIEPER, ANDREW A · 2021 to 2025
$6.9M
Neuroprotective actions of cystathionine g-lyase through gasotransmitter hydrogen sulfide signalingR01AG071512 · NIA · JOHNS HOPKINS UNIVERSITY · PI Bindu Paul · 2022 to 2026
$3.4M
Mechanism of white matter pathology in Alzheimer's diseaseR01AG076051 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI XIN QI · 2022 to 2026
$3.0M
Regulation of ATAD3A in TDP43-associated ALS/FTDR01NS141199 · NINDS · CASE WESTERN RESERVE UNIVERSITY · PI XIN QI · 2025 to 2026
$1.5M
Regulation of CHCHD6 in Alzheimer's diseaseR01AG074346 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI XIN QI · 2025 to 2026
$1.4M
Role of sulfhydration on the functions of the microtubule associated protein, TauR21AG073684 · NIA · JOHNS HOPKINS UNIVERSITY · PI PAUL, BINDU · 2021 to 2022
$450k
BLRD VA I01 BX005976NIA NIH HHS R01 AG071512NIA NIH HHS R01 AG074346NIA NIH HHS R01 AG076051NIA NIH HHS R21 AG073684NIGMS NIH HHS RM1 GM142002NINDS NIH HHS R01 NS141199
6 · The paper itself

Abstract

The prostaglandin- and autocoid-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is shown here to be pathologically elevated in Parkinson's disease (PD) patients and mouse models of PD in the substantia nigra, the region of the brain where dopaminergic neurons are lost in PD. Inhibiting 15-PGDH by pharmacologic blockade or partial genetic reduction restores redox homeostasis and mitigates microglial and astrocyte activation, dopaminergic neuron loss, and motor impairment across three mouse models of PD. These models included systemic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), intranigral lipopolysaccharide (LPS), and intrastriatal AAV-α-synuclein with intra-ventral tegmental area α-synuclein preformed fibrils (PFFs). The neuroprotective efficacy of 15-PGDH inhibition in PD is shown to be mediated by downregulation of the dopaminergic neuronal cell death mediator lipocalin-2 (Lcn2), the pro-inflammatory cytokine interleukin-1β, the reactive oxygen generator Cybb/Nox2, and oxidative tissue damage. Mechanistically, in vitro exposure of BV2 microglia to LPS recapitulates induction of Lcn2, Cybb/N OX2 and superoxide, and all three of these effects are reversed by co-treating with prostaglandin E2 (PGE2), the prototypical degradation substrate of 15-PGDH. With a 15-PGDH inhibitor (MF-300) currently in human clinical trials for peripheral indications, these findings have translational relevance for PD.

Indexed as

Hydroxyprostaglandin DehydrogenasesNeuroprotectionNeuroprotective AgentsParkinson DiseaseAnimalsDisease Models, AnimalDopaminergic NeuronsHomeostasisHumansMaleMiceMicrogliaOxidation-ReductionOxidative Stress15-hydroxyprostaglandin dehydrogenaseHydroxyprostaglandin DehydrogenasesNeuroprotective Agents15-Hydroxyprostaglandin dehydrogenaseNeuroprotectionOxidative stressParkinson's diseaseReactive oxygen speciesSW033291

Identifiers

PMID42398271
PMCPMC13351393

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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.