Evidence map›Paper›PMID 39737939›Full record

ArticleNature communications2024

DLK-dependent axonal mitochondrial fission drives degeneration after axotomy.

Jorge Gómez-Deza, Matthew Nebiyou, Mor R Alkaslasi, Francisco M Nadal-Nicolás, Preethi Somasundaram, Anastasia L Slavutsky, Wei Li, Michael E Ward, Trent A Watkins, Claire E Le Pichon

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Jorge Gómez-DezaEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Matthew NebiyouEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Mor R AlkaslasiEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0001-6298-885X
Francisco M Nadal-NicolásNational Eye Institute, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0003-4121-514X
Preethi SomasundaramDepartment of Neurosurgery, Baylor College of Medicine, Houston, TX, USA.
Anastasia L SlavutskyEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Wei LiNational Eye Institute, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-2897-649X
Michael E WardNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Trent A WatkinsDepartment of Neurosurgery, Baylor College of Medicine, Houston, TX, USA.ORCID 0000-0001-6723-3712
Claire E Le PichonEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. claire.lepichon@nih.gov.ORCID 0000-0002-9274-3615

Funding

Mechanisms of inherited neurodegenerative diseasesZIANS003155 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI WARD, MICHAEL · 2016 to 2025
$24.7M
Functions of the Synaptic Ribbon in Retinal NeuronsZIAEY000488 · NEI · NATIONAL EYE INSTITUTE · PI LI, WEI · 2009 to 2025
$22.0M
UCSF IRACDA Scholars ProgramK12GM081266 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Raymond M. Esquerra, HOLLY A. INGRAHAM · 2007 to 2026
$19.4M
The neuronal stress response in neurodegenerative disease and painZIAHD008966 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI LE PICHON, CLAIRE · 2017 to 2025
$17.1M
The integrated stress response in cognitive disordersR01NS076708 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI PFAFFINGER, PAUL, RAY, RUSSELL S · 2012 to 2025
$7.9M
MOLECULAR DISSECTION OF THE AXONAL INJURY RESPONSE FOR REGENERATION AND NEUROPROTECTIONR01NS112691 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WATKINS, TRENT · 2020 to 2024
$1.9M
Intramural NIH HHS ZIA EY000488Intramural NIH HHS ZIA HD008966Intramural NIH HHS ZIA NS003155NIGMS NIH HHS K12 GM081266NINDS NIH HHS R01 NS076708NINDS NIH HHS R01 NS112691U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) ZIA-HD008966U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI) ZIAEY000488U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) 1ZIANS003155-03
6 · The paper itself

Abstract

Currently there are no effective treatments for an array of neurodegenerative disorders to a large part because cell-based models fail to recapitulate disease. Here we develop a reproducible human iPSC-based model where laser axotomy causes retrograde axon degeneration leading to neuronal cell death. Time-lapse confocal imaging revealed that damage triggers an apoptotic wave of mitochondrial fission proceeding from the site of injury to the soma. We demonstrate that this apoptotic wave is locally initiated in the axon by dual leucine zipper kinase (DLK). We find that mitochondrial fission and resultant cell death are entirely dependent on phosphorylation of dynamin related protein 1 (DRP1) downstream of DLK, revealing a mechanism by which DLK can drive apoptosis. Importantly, we show that CRISPR mediated Drp1 depletion protects mouse retinal ganglion neurons from degeneration after optic nerve crush. Our results provide a platform for studying degeneration of human neurons, pinpoint key early events in damage related neural death and provide potential focus for therapeutic intervention.

Indexed as

ApoptosisAxonsAxotomyDynaminsInduced Pluripotent Stem CellsMitochondrial DynamicsRetinal Ganglion CellsAnimalsHumansMAP Kinase Kinase KinasesMiceNerve CrushNerve DegenerationOptic Nerve InjuriesPhosphorylationDNM1L protein, humanDynaminsMAP Kinase Kinase Kinasesmitogen-activated protein kinase kinase kinase 12

Identifiers

PMID39737939
PMCPMC11686342

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.