Evidence map›Paper›PMID 40422188›Full record

ArticleCells2025

Retinoid X Receptor as a Therapeutic Target to Treat Neurological Disorders Associated with α-Synucleinopathy.

Assylbek Zhylkibayev, Christopher R Starr, M Iqbal Hossain, Sandeep Kumar, Shaida A Andrabi, Maria B Grant, Venkatram R Atigadda, Marina S Gorbatyuk, Oleg S Gorbatyuk

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cells, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Assylbek ZhylkibayevDepartment of Biochemistry, School of Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.ORCID 0000-0001-9244-1505
Christopher R StarrDepartment of Ophthalmology, School of Medicine, University of Alabama, Birmingham, AL 35233, USA.ORCID 0000-0002-2038-481X
M Iqbal HossainDepartment of Pharmacology and Toxicology, School of Medicine, University of Alabama, Birmingham, AL 35294, USA.ORCID 0000-0002-8587-4131
Sandeep KumarDepartment of Biochemistry, School of Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.
Shaida A AndrabiDepartment of Pharmacology and Toxicology, School of Medicine, University of Alabama, Birmingham, AL 35294, USA.
Maria B GrantDepartment of Ophthalmology, School of Medicine, University of Alabama, Birmingham, AL 35233, USA.
Venkatram R AtigaddaDepartment of Dermatology, Heersink School of Medicine, University of Alabama, Birmingham, AL 35233, USA.ORCID 0000-0003-0085-0403
Marina S GorbatyukDepartment of Biochemistry, School of Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.ORCID 0000-0001-9060-856X
Oleg S GorbatyukDepartment of Translational Neuroscience, School of Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.

Funding

VISION SCIENCE RESEARCH CENTERP30EY003039 · NEI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI GAMLIN, PAUL DOUGLAS · 1985 to 2025
$15.4M
NITRIC OXIDE IN THE PATHOGENESIS OF DIABETIC RETINOPATHYR01EY012601 · NEI · UNIVERSITY OF FLORIDA · PI Julia V Busik, Maria Bartolomeo Grant · 1998 to 2026
$9.6M
ACE2 on gut barrier dysfunction and BRB disruptionR01EY032753 · NEI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Michael Edwin Boulton, Maria Bartolomeo Grant · 2022 to 2026
$1.8M
RXR-based therapy for diabetic retinopathyR01EY035539 · NEI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI Marina Gorbatyuk, Maria Bartolomeo Grant · 2024 to 2026
$1.7M
NEI NIH HHS P30 EY003039NEI NIH HHS R01 EY012601NEI NIH HHS R01 EY032753NEI NIH HHS R01 EY035539
6 · The paper itself

Abstract

This study investigated the therapeutic potential of the nuclear retinoid X receptor (RXR) in mitigating the progression of alpha-synucleinopathies (αSNPs), particularly in Parkinson's disease (PD). PD-like pathology in mice was successfully induced through the co-delivery of AAV expressing human α-synuclein (αS) and αS preformed fibrils (PFFs) into the substantia nigra pars compacta (SNpc). Significant increases in Lewy body (LB)-like inclusions, loss of tyrosine hydroxylase-positive (TH+) neurons, and reductions in dopamine (DA) levels in the striatum were observed. Additionally, diminished levels of PPARα and NURR1-proteins essential for neuronal survival-along with elevated expression of IBA1 and GFAP, markers of microglial activation and astrocytic gliosis, respectively, are associated with the pathogenesis of Parkinson's disease. AAV-mediated overexpression of human RXRα demonstrated preservation of TH+ neurons, prevention of DA decline, and attenuation of αS accumulation. Furthermore, RXR-treated PD brains showed a reduced number of GFAP+ and Iba1+ cells, decreased GFAP+ and IBA1+ immunoreactivity, and fewer and less widespread LB-like aggregates. RXR overexpression also enhanced the production of PPARα and NURR1. These findings suggest that RXRα upregulation promotes neuroprotection by mitigating αSNPs and chronic neuroinflammation, a major contributor to PD progression. This research underscores the therapeutic potential of targeting nuclear receptors, such as RXR, in neurodegenerative diseases like PD.

Indexed as

alpha-SynucleinParkinson DiseaseRetinoid X Receptor alphaRetinoid X ReceptorsSynucleinopathiesAnimalsDopamineDopaminergic NeuronsHumansMaleMiceMice, Inbred C57BLMicrogliaNeuronsNuclear Receptor Subfamily 4, Group A, Member 2PPAR alphaalpha-SynucleinDopamineNuclear Receptor Subfamily 4, Group A, Member 2PPAR alphaRetinoid X Receptor alphaRetinoid X ReceptorsTyrosine 3-MonooxygenasedopamineinflammationLewy bodyNURR1Parkinson’s diseasePPARαretinoid X receptorα-synucleinα-synucleinopathy

Identifiers

PMID40422188
PMCPMC12109830

What OpenQuestion holds

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Registered trials

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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.