Evidence map›Paper›PMID 40670678›Full record

ArticleMolecular psychiatry2025

TRAF6 regulates ubiquitination-independent TDP-43 condensation and related neurodegeneration.

Shupan Guo, Xueyin Zu, Fei Tang, Aolan Zhou, Xinru Yan, Zhihui Zhou, Xin Liu, Pan Li, Shiqian Qi, Wei Cheng and 2 more

Abstract read
PubMed Publisher
In one paragraph

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

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0cells of the map it votes in
0citing papers in PubMed
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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

12 authors.

Shupan Guo *Department of Pulmonary and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-related Molecular Network, and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, China.
Xueyin Zu *Department of Pulmonary and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-related Molecular Network, and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, China.
Fei Tang *Department of Neurology and State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, China.
Aolan Zhou *Department of Pulmonary and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-related Molecular Network, and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, China.
Xinru YanDepartment of Pulmonary and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-related Molecular Network, and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, China.
Zhihui ZhouDepartment of Pulmonary and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-related Molecular Network, and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, China.
Xin LiuDepartment of Pulmonary and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-related Molecular Network, and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, China.
Pan LiDepartment of Pulmonary and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-related Molecular Network, and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, China.ORCID http://orcid.org/0000-0002-6810-2367
Shiqian QiDepartment of Pulmonary and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-related Molecular Network, and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, China.ORCID http://orcid.org/0000-0002-7589-8877
Wei ChengDepartment of Pulmonary and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-related Molecular Network, and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, China.
Peng LeiDepartment of Neurology and State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, China. peng.lei@scu.edu.cn.ORCID http://orcid.org/0000-0001-5652-1962
Haiyan RenDepartment of Pulmonary and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-related Molecular Network, and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, China. hyren@scu.edu.cn.ORCID http://orcid.org/0000-0001-9995-3255

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cytoplasmic aggregates of TDP-43 are hallmarks of multiple neurodegenerative diseases. However, the underlying mechanisms driving TDP-43 pathological aggregation remain elusive. In this study, we revealed that TNF receptor-associated factor 6 (TRAF6) promotes TDP-43 condensation, and disrupting TRAF6-TDP-43 interactions effectively suppresses its aggregation. Our findings reveal that TRAF6 expression increases during senescence and preferentially interacts with RNA-binding-deficient TDP-43, a variant associated with neurotoxicity. Importantly, TRAF6 facilitates TDP-43 aggregation through a mechanism independent of its E3 ligase activity. Furthermore, we identified the motif of TDP-43 responsible for its interaction with TRAF6, enabling the design of a peptide inhibitor. This peptide effectively reduces pathological TDP-43 aggregation in cells and alleviates movement disorders and cognitive decline in mouse models. Together, these results establish a direct link between TRAF6 and TDP-43 neurotoxicity, emphasizing TRAF6's role in driving TDP-43 pathology, and position TRAF6 as a promising target for combating TDP-43-related neurodegenerative diseases.

Indexed as

DNA-Binding ProteinsTNF Receptor-Associated Factor 6AnimalsDisease Models, AnimalHEK293 CellsHumansIntracellular Signaling Peptides and ProteinsMiceMice, Inbred C57BLNeurodegenerative DiseasesProtein Aggregation, PathologicalUbiquitinationDNA-Binding ProteinsIntracellular Signaling Peptides and ProteinsTARDBP protein, humanTardbp protein, mouseTifab protein, humanTNF Receptor-Associated Factor 6

Identifiers

PMID40670678

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.