Evidence map›Paper›PMID 39803527›Full record

ArticlebioRxiv : the preprint server for biology2025

Maintenance of neuronal TDP-43 expression requires axonal lysosome transport.

Veronica H Ryan, Sydney Lawton, Joel F Reyes, James Hawrot, Ashley M Frankenfield, Sahba Seddighi, Daniel M Ramos, Jacob Epstein, Faraz Faghri, Nicholas L Johnson and 10 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

20 authors.

Veronica H RyanNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Sydney LawtonNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Joel F ReyesNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
James HawrotNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Ashley M FrankenfieldDepartment of Chemistry, George Washington University, Washington, DC, USA.
Sahba SeddighiNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Daniel M RamosCenter for Alzheimer's and Related Dementias, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Jacob EpsteinCenter for Alzheimer's and Related Dementias, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Faraz FaghriCenter for Alzheimer's and Related Dementias, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Nicholas L JohnsonCenter for Alzheimer's and Related Dementias, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Jizhong ZouNational Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Martin KampmannInstitute for Neurodegenerative Diseases, Weill Institute for Neurosciences, and Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-3819-7019
John ReplogleNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Yue A QiCenter for Alzheimer's and Related Dementias, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Hebao YuanNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0003-4425-3678
Kory R JohnsonNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Dragan MaricNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Ling HaoDepartment of Chemistry and Biochemistry, University of Maryland, College Park, MD, USA.
Mike A NallsCenter for Alzheimer's and Related Dementias, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Michael E WardNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-5296-8051

Funding

NINDS NIH HHS R01 NS121608
6 · The paper itself

Abstract

TDP-43 mislocalization and pathology occurs across a range of neurodegenerative diseases, but the pathways that modulate TDP-43 in neurons are not well understood. We generated a Halo-TDP-43 knock-in iPSC line and performed a genome-wide CRISPR interference FACS-based screen to identify modifiers of TDP-43 levels in neurons. A meta-analysis of our screen and publicly available screens identified both specific hits and pathways present across multiple screens, the latter likely responsible for generic protein level maintenance. We identified BORC, a complex required for anterograde lysosome transport, as a specific modifier of TDP-43 protein, but not mRNA, levels in neurons. BORC loss led to longer half-life of TDP-43 and other proteins, suggesting lysosome location is required for proper protein turnover. As such, lysosome location and function are crucial for maintaining TDP-43 protein levels in neurons.

Identifiers

PMID39803527
PMCPMC11722429

What Socratic holds

Textmetadata
LicenceCC0
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 Socratic graph.