Evidence map›Paper›PMID 41258081›Full record

ArticleExperimental & molecular medicine2025

Redirecting microglia phenotype via inhibition of NFAT1 ameliorates deficits in mouse model of synucleinopathies.

Michiyo Iba, Yeon-Joo Lee, Somin Kwon, Liam Horan-Portelance, Katherine Chang, Minhyung Kim, Natalie Landeck, Robert A Rissman, Seung-Jae Lee, Sungyong You and 1 more

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In one paragraph

Article in Experimental & molecular medicine, 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. 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

11 authors.

Michiyo Iba *Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Yeon-Joo Lee *Departments of Urology and Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-6605-8761
Somin KwonInternal Medicine Residency Program, Walter Reed National Military Medical Center, Bethesda, MD, USA.
Liam Horan-PortelanceCell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-7237-7574
Katherine ChangCell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Minhyung KimDepartments of Urology and Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Natalie LandeckNeurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Robert A RissmanDepartment Neurosciences, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
Seung-Jae LeeDepartment of Biomedical Sciences, Neuroscience Research Institute and Department of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Sungyong YouDepartments of Urology and Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Sungyong.You@cshs.org.ORCID http://orcid.org/0000-0003-3513-1783
Changyoun KimCell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. changyoun.kim@nih.gov.ORCID http://orcid.org/0000-0001-9936-8195

Funding

U.S. Department of Defense (United States Department of Defense) PC190482
6 · The paper itself

Abstract

The abnormal deposition of α-synuclein (α-syn) and neuroinflammation are key features of synucleinopathies. We recently demonstrated that leucine-rich repeat kinase 2 (LRRK2) and nuclear factor of activated T cells 1 (NFAT1) modulate the neurotoxic inflammation in synucleinopathies mediated by microglia. Therefore, we hypothesized that targeting NFAT1 might ameliorate the microglial neurotoxicity in synucleinopathies. Here we utilized 11R-VIVIT, an NFAT1 inhibitory peptide, in in vivo, ex vivo and in vitro synucleinopathy models to evaluate the effects of NFAT1 inhibition to test this hypothesis. The microglia in synucleinopathy mouse models become excessively activated due to chronic disease conditions, thereby increasing the expressions of proinflammatory cytokines in these cells and decreasing the expressions of genes associated with microglial mobility and phagocytosis, strongly associated with neurodegeneration and pathogenic α-syn deposition. However, we observed that the inhibition of NFAT1 decreased the microglial neuroinflammation, thereby ameliorating neurodegeneration and α-syn neuropathology in vivo. Furthermore, the comprehensive in vivo transcriptomic analysis of the microglia revealed that the inhibition of NFAT1 restored their mobility and phagocytic abilities via upregulations of related genes. Our study proposes that the inhibition of NFAT1 redirects the excessively activated microglia to active healthy microglia, thereby reducing synucleinopathy neurotoxicity.

Indexed as

MicrogliaNFATC Transcription FactorsSynucleinopathiesalpha-SynucleinAnimalsDisease Models, AnimalHumansMicePhagocytosisPhenotypealpha-SynucleinNFATC Transcription Factors

Identifiers

PMID41258081
PMCPMC12686539

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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.