Evidence map›Paper›PMID 41444620›Full record

ArticleActa neuropathologica communications2025

PPAR-γ activation by pioglitazone inhibits microglia-mediated neuroinflammation and alleviates disease in neuromyelitis optica spectrum disorders.

Leung Wah Yick, Ethel Yin Ying Chan, Wenying Zou, Krystal Xiwing Yau, Jason Shing Cheong Kwan, Chi Yan Lee, Koon Ho Chan

Abstract read
In one paragraph

Article in Acta neuropathologica communications, 2025. 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. 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

7 authors.

Leung Wah YickDepartment of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 4/F Professorial Block, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China.
Ethel Yin Ying ChanDepartment of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 4/F Professorial Block, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China.
Wenying ZouDepartment of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 4/F Professorial Block, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China.
Krystal Xiwing YauDepartment of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 4/F Professorial Block, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China.
Jason Shing Cheong KwanDepartment of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 4/F Professorial Block, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China.
Chi Yan LeeDepartment of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 4/F Professorial Block, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China.
Koon Ho ChanDepartment of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 4/F Professorial Block, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China. koonho@hku.hk.

Funding

Health & Medical Research Fund, Food and Health Bureau, Hong Kong 08192726
6 · The paper itself

Abstract

Microglia contribute to antibody-dependent cell-mediated cytotoxicity (ADCC) in neuromyelitis optica spectrum disorders (NMOSD). This complement-independent process has been implicated in early neuroinflammation following aquaporin-4 immunoglobulin G autoantibodies (AQP4-IgG) binding to astrocytes. We investigated whether pioglitazone, a clinically approved peroxisome proliferator-activated receptor gamma (PPARγ) agonist, could be repurposed to reduce complement-independent neuroinflammation driven by activated microglia and ameliorate disease in mice receiving passive transfers of human AQP4-IgG. Pioglitazone treatment alleviated motor impairments and NMOSD-like pathologies, associating with reduced microglial activation and pro-inflammatory cytokine levels. Antagonizing PPARγ reversed the beneficial effects of pioglitazone, indicating that these effects were PPARγ-dependent. Microglial depletion attenuated AQP4-IgG-induced motor impairments and pathologies, supporting the detrimental role of microglial activation. Serum levels of soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a microglial activation biomarker, were increased in both the mouse model and patients with NMOSD. Pioglitazone reduced sTREM2, which were correlated with attenuated AQP4-IgG-induced microglial activation, neuroinflammation, and pathologies in mice. Elevated sTREM2 levels were associated with cytokines and chemokines related to activated microglia in patients with NMOSD, suggesting the clinical benefits of pioglitazone. Our findings highlight the potential of repurposing PPAR-γ agonists for reducing microglia-mediated neuroinflammation in acute NMOSD attacks.

Indexed as

MicrogliaNeuroinflammatory DiseasesNeuromyelitis OpticaPioglitazonePPAR gammaAnimalsAquaporin 4Disease Models, AnimalFemaleHumansImmunoglobulin GMaleMiceMice, Inbred C57BLPPAR-gamma AgonistsAquaporin 4Immunoglobulin GPioglitazonePPAR gammaPPAR-gamma AgonistsMicrogliaNeuroinflammationNeuromyelitis opticaPioglitazonePPAR-γ agonist

Identifiers

PMID41444620
PMCPMC12729228

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.