Evidence map›Paper›PMID 39975323›Full record

ArticlebioRxiv : the preprint server for biology2025

Nemo-like kinase disrupts nuclear import and drives TDP43 mislocalization in ALS.

Michael E Bekier, Emile Pinarbasi, Jack J Mesojedec, Layla Ghaffari, Martina de Majo, Erik Ullian, Mark Koontz, Sarah Coleman, Xingli Li, Elizabeth M H Tank and 2 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

5 · Who and what money

Authors and funding

12 authors.

Michael E BekierDepartment of Neurology, University of Michigan, Ann Arbor, MI, 48109, United States.ORCID 0000-0002-0886-3105
Emile PinarbasiDepartment of Neurology, University of Michigan, Ann Arbor, MI, 48109, United States.ORCID 0000-0001-6313-483X
Jack J MesojedecDepartment of Neurology, University of Michigan, Ann Arbor, MI, 48109, United States.
Layla GhaffariSynapticure, Chicago, IL, United States 60612.ORCID 0000-0003-1573-7745
Martina de MajoSynapticure, Chicago, IL, United States 60612.ORCID 0000-0003-4524-6293
Erik UllianDepartment of Ophthalmology & Physiology, University of California San Francisco, San Francisco, CA, 94143, United States.ORCID 0000-0003-2077-8584
Mark KoontzSynapticure, Chicago, IL, United States 60612.ORCID 0000-0001-5390-9515
Sarah ColemanSynapticure, Chicago, IL, United States 60612.
Xingli LiDepartment of Neurology, University of Michigan, Ann Arbor, MI, 48109, United States.
Elizabeth M H TankDepartment of Neurology, University of Michigan, Ann Arbor, MI, 48109, United States.
Jacob WaksmackiDepartment of Neurology, University of Michigan, Ann Arbor, MI, 48109, United States.ORCID 0009-0002-7876-779X
Sami BarmadaDepartment of Neurology, University of Michigan, Ann Arbor, MI, 48109, United States.ORCID 0000-0002-9604-968X

Funding

Michigan Institute for Clinical and Health Research (MCHR)UL1TR000433 · NCATS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MASHOUR, GEORGE ALEXANDER · 2012 to 2016
$49.9M
Research Education ComponentP30AG072931 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Henry L Paulson · 2021 to 2026
$26.5M
RNA decay in amyotrophic lateral sclerosis and frontotemporal lobar degenerationR01NS097542 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BARMADA, SAMI · 2016 to 2025
$3.8M
Novel patient-derived 3D platform for detecting TDP-43 proteinopathy and associated biomarkers for ALS/FTDR44NS124457 · NINDS · SYNAPTICURE, INC. · PI GHAFFARI, LAYLA, ULLIAN, ERIK M · 2022 to 2023
$2.2M
Atypical TDP43 isoforrms driving neurodegeneration in FTD/ALSR01NS113943 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BARMADA, SAMI · 2020 to 2024
$1.9M
Spatiotemporal analysis of TDP-43 toxicity and endolysosomal turnover mechanismsR56NS128110 · NINDS · UNIVERSITY OF ARIZONA · PI BARMADA, SAMI, BUCHAN, JOHN ROSS · 2022 to 2022
$393k
NCATS NIH HHS UL1 TR000433NIA NIH HHS P30 AG072931NINDS NIH HHS R01 NS097542NINDS NIH HHS R01 NS113943NINDS NIH HHS R44 NS124457NINDS NIH HHS R56 NS128110
6 · The paper itself

Abstract

Cytoplasmic TDP43 mislocalization and aggregation are pathological hallmarks of amyotrophic lateral sclerosis (ALS). However, the initial cellular insults that lead to TDP43 mislocalization remain unclear. In this study, we demonstrate that Nemo-like kinase (NLK)-a proline-directed serine/threonine kinase-promotes the mislocalization of TDP43 and other RNA-binding proteins by disrupting nuclear import. NLK levels are selectively elevated in neurons exhibiting TDP43 mislocalization in ALS patient tissues, while genetic reduction of

Identifiers

PMID39975323
PMCPMC11838369

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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.