Evidence map›Paper›PMID 40019378›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

Accumulation of Damaging Lipids in the Arf1-Ablated Neurons Promotes Neurodegeneration through Releasing mtDNA and Activating Inflammatory Pathways in Microglia.

Xu Li, Shuhan Jin, Danke Wang, Ying Wu, Xiaoyu Tang, Yufan Liu, Tiange Yao, Shoufa Han, Lin Sun, Yuetong Wang and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Lipophagy and lipid droplets in neurodegeneration.Trends in pharmacological sciences · 2026
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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.

Xu LiDepartment of Cell and Developmental Biology at School of Life Sciences, State Key Laboratory of Genetic Engineering, Institute of Metabolism and Integrative Biology, Children's Hospital, Zhongshan Hospital, Fudan University, Shanghai, 200438, China.ORCID https://orcid.org/0009-0009-1013-0208
Shuhan JinDepartment of Cell and Developmental Biology at School of Life Sciences, State Key Laboratory of Genetic Engineering, Institute of Metabolism and Integrative Biology, Children's Hospital, Zhongshan Hospital, Fudan University, Shanghai, 200438, China.
Danke WangDepartment of Cell and Developmental Biology at School of Life Sciences, State Key Laboratory of Genetic Engineering, Institute of Metabolism and Integrative Biology, Children's Hospital, Zhongshan Hospital, Fudan University, Shanghai, 200438, China.
Ying WuDepartment of Cell and Developmental Biology at School of Life Sciences, State Key Laboratory of Genetic Engineering, Institute of Metabolism and Integrative Biology, Children's Hospital, Zhongshan Hospital, Fudan University, Shanghai, 200438, China.
Xiaoyu TangDepartment of Cell and Developmental Biology at School of Life Sciences, State Key Laboratory of Genetic Engineering, Institute of Metabolism and Integrative Biology, Children's Hospital, Zhongshan Hospital, Fudan University, Shanghai, 200438, China.
Yufan LiuDepartment of Cell and Developmental Biology at School of Life Sciences, State Key Laboratory of Genetic Engineering, Institute of Metabolism and Integrative Biology, Children's Hospital, Zhongshan Hospital, Fudan University, Shanghai, 200438, China.
Tiange YaoDepartment of Cell and Developmental Biology at School of Life Sciences, State Key Laboratory of Genetic Engineering, Institute of Metabolism and Integrative Biology, Children's Hospital, Zhongshan Hospital, Fudan University, Shanghai, 200438, China.
Shoufa HanState Key Laboratory for Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, The Key Laboratory for Chemical Biology of Fujian Province, The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Innovation Center for Cell Signalling Network, Xiamen University, Xiamen, 361005, China.
Lin SunDepartment of Cell and Developmental Biology at School of Life Sciences, State Key Laboratory of Genetic Engineering, Institute of Metabolism and Integrative Biology, Children's Hospital, Zhongshan Hospital, Fudan University, Shanghai, 200438, China.
Yuetong WangDepartment of Cell and Developmental Biology at School of Life Sciences, State Key Laboratory of Genetic Engineering, Institute of Metabolism and Integrative Biology, Children's Hospital, Zhongshan Hospital, Fudan University, Shanghai, 200438, China.
Steven X HouDepartment of Cell and Developmental Biology at School of Life Sciences, State Key Laboratory of Genetic Engineering, Institute of Metabolism and Integrative Biology, Children's Hospital, Zhongshan Hospital, Fudan University, Shanghai, 200438, China.ORCID https://orcid.org/0000-0001-7583-2504

Funding

National Key Research and Development Program of China 2023YFA1800202National Natural Science Foundation of China 82203511National Natural Science Foundation of China 82450108National Natural Science Foundation of China 82472817
6 · The paper itself

Abstract

Lipid metabolism disorders in both neurons and glial cells have been found in neurodegenerative (ND) patients and animal models. However, the pathological connection between lipid droplets and NDs remains poorly understood. The recent work has highlighted the utility of a neuron-specific Arf1-knockout mouse model and corresponding cells for elucidating the nexus between lipid metabolism disorders and amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). In this study, it is found that Arf1 deficiency first induced surplus fatty acid synthesis through the AKT-mTORC1-SREBP1-FASN axis, which further triggered endoplasmic reticulum (ER)-mitochondrial stress cascade via calcium flux. The organelle stress cascade further caused mitochondrial DNA (mtDNA) to be released into cytoplasm. Concurrently, the FASN-driven fatty acid synthesis in the Arf1-deficient neurons might also induce accumulation of sphingolipids in lysosomes that caused dysfunction of autophagy and lysosomes, which further promoted lysosomal stress and mitochondria-derived extracellular vesicles (MDEVs) release. The released MDEVs carried mtDNA into microglia to activate the inflammatory pathways and neurodegeneration. The studies on neuronal lipid droplets (LDs) and recent studies of microglial LDs suggest a unified pathological function of LDs in NDs: activating the inflammatory pathways in microglia. This finding potentially provides new therapeutic strategies for NDs.

Indexed as

ADP-Ribosylation Factor 1DNA, MitochondrialInflammationLipid MetabolismMicrogliaNeurodegenerative DiseasesNeuronsAnimalsAutophagyEndoplasmic Reticulum StressMiceMice, KnockoutMitochondriaADP-Ribosylation Factor 1DNA, Mitochondrialaccumulation of damaging lipidsArf1 ablationmtDNA releaseneurodegeneration

Identifiers

PMID40019378
PMCPMC12021055

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.