Evidence map›Paper›PMID 41279943›Full record

ArticlebioRxiv : the preprint server for biology2025

Labile iron overload reprograms microglia and neurons for lipid droplet synthesis in the aging brain.

Karina Cunha E Rocha, Qian Xiang, Chengjia Qian, Lishuan Wang, Wei Yuan, Varsha Beldona, Ying Duan, Luana Veras, Darya Abolmaali, Garam An and 4 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 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

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

14 authors.

Karina Cunha E RochaDepartment of Medicine, Division of Endocrinology & Metabolism, University of California, San Diego; La Jolla, California, USA.
Qian XiangDivision of Biological Sciences, University of California, San Diego; La Jolla, California, USA.
Chengjia QianDivision of Biological Sciences, University of California, San Diego; La Jolla, California, USA.
Lishuan WangDepartment of Medicine, Division of Endocrinology & Metabolism, University of California, San Diego; La Jolla, California, USA.
Wei YuanDepartment of Medicine, Division of Endocrinology & Metabolism, University of California, San Diego; La Jolla, California, USA.
Varsha BeldonaDivision of Biological Sciences, University of California, San Diego; La Jolla, California, USA.
Ying DuanDivision of Biological Sciences, University of California, San Diego; La Jolla, California, USA.
Luana VerasDivision of Biological Sciences, University of California, San Diego; La Jolla, California, USA.
Darya AbolmaaliDivision of Biological Sciences, University of California, San Diego; La Jolla, California, USA.
Garam AnDepartment of Medicine, Division of Endocrinology & Metabolism, University of California, San Diego; La Jolla, California, USA.
Junho ParkDepartment of Medicine, Division of Endocrinology & Metabolism, University of California, San Diego; La Jolla, California, USA.
Whasun LimDepartment of Medicine, Division of Endocrinology & Metabolism, University of California, San Diego; La Jolla, California, USA.
Xu ChenDepartment of Neurosciences, University of California San Diego, La Jolla, CA, United States of America.
Wei YingDepartment of Medicine, Division of Endocrinology & Metabolism, University of California, San Diego; La Jolla, California, USA.

Funding

UCLA LIFT-UP (Leveraging Institutional support For Talented, Upcoming Physicians and/or Scientists)U24DK132746 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI OBIDIUGWU KENRIK DURU, CAROL M MANGIONE · 2022 to 2026
$3.2M
Mechanisms by which the ketone body β-hydroxybutyrate counteracts tau pathogenesisR01AG074273 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Xu Chen · 2022 to 2026
$2.7M
Role of Testosterone in Modulating Tau Pathogenesis in FemalesR01AG078185 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Xu Chen · 2022 to 2026
$2.7M
Mechanisms by which hepatocyte extracellular miRNAs mediate peripheral insulin sensitivityR01DK125560 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI YING, WEI · 2021 to 2025
$2.0M
Illumina NovaSeq 6000 Sequencing SystemS10OD026929 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEPSEN, KRISTEN LYNN · 2019 to 2019
$600k
NIA NIH HHS R01 AG074273NIA NIH HHS R01 AG078185NIDDK NIH HHS R01 DK125560NIDDK NIH HHS U24 DK132746NIH HHS S10 OD026929
6 · The paper itself

Abstract

Lipid-droplet (LD) accumulation emerges in microglia and neurons with age. Because neither cell type is specialized for lipid storage, LDs are linked to dysfunction. The upstream drivers of LD formation and their effects on neighboring cells remain unclear. Here, we identify a mitochondrial-iron axis that promotes LD formation in aging microglia via reactive oxygen species (ROS), which secondarily reshapes neuronal iron handling. LD-enriched microglia show reduced mitochondrial mass and increased labile iron, ROS, and lipid peroxidation. Chelating labile iron or scavenging ROS suppresses LD formation. Conditioned media from iron-stressed microglia alter neuronal iron homeostasis, indicating transcellular coupling. In primary neurons, iron overload increases LDs and activates coordinated iron, ROS, and lipogenesis programs, whereas antioxidant treatment attenuates iron-driven LD accumulation. Together, these findings position iron overload as an upstream regulator of ROS-dependent LD biogenesis in microglia and neurons and reveal a microglia-neuron axis that regulates neuronal iron metabolism during aging.

Identifiers

PMID41279943
PMCPMC12637668

What OpenQuestion holds

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LicenceCC BY-NC
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.