ArticlebioRxiv : the preprint server for biology2024
DLK-dependent axonal mitochondrial fission drives degeneration following axotomy.
Jorge Gómez-Deza, Matthew Nebiyou, Mor R Alkaslasi, Francisco M Nadal-Nicolás, Preethi Somasundaran, Anastasia L Slavutsky, Michael E Ward, Wei Li, Trent A Watkins, Claire E Le Pichon
Open access · greenAbstract readPreprint
In one paragraphArticle in bioRxiv : the preprint server for biology, 2024. 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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What it found
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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 registryThe trial behind it
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3 · Its place in the literatureWho cites it
0 citing papers in PubMed, 2 citations in OpenAlex.
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4 · The recordCorrections and comments
5 · Who and what moneyAuthors and funding
10 authors at 3 institutions in 1 country.
Jorge Gómez-DezaEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States.
Matthew NebiyouEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States.
Mor R AlkaslasiEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States.
Francisco M Nadal-NicolásNational Eye Institute, National Institutes of Health, Bethesda, United States.
Preethi SomasundaranDepartment of Neurosurgery, Baylor College of Medicine, Houston, TX.
Anastasia L SlavutskyEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States.
Michael E WardNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States.ORCID 0000-0002-5296-8051 Trent A WatkinsDepartment of Neurosurgery, Baylor College of Medicine, Houston, TX.
Claire E Le PichonEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States.ORCID 0000-0002-9274-3615 National Institutes of Health · USBaylor College of Medicine · USUniversity of California, San Francisco · US
Funding
Mechanisms of inherited neurodegenerative diseasesZIANS003155 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI WARD, MICHAEL · 2016 to 2025
$24.7MFunctions of the Synaptic Ribbon in Retinal NeuronsZIAEY000488 · NEI · NATIONAL EYE INSTITUTE · PI LI, WEI · 2009 to 2025
$22.0MThe 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
$17.1MThe integrated stress response in cognitive disordersR01NS076708 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI PFAFFINGER, PAUL, RAY, RUSSELL S · 2012 to 2025
$7.9MMOLECULAR DISSECTION OF THE AXONAL INJURY RESPONSE FOR REGENERATION AND NEUROPROTECTIONR01NS112691 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WATKINS, TRENT · 2020 to 2024
$1.9MIntramural NIH HHS ZIA EY000488Intramural NIH HHS ZIA HD008966Intramural NIH HHS ZIA NS003155NINDS NIH HHS R01 NS112691
6 · The paper itselfAbstract
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 developed 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 demonstrated that this apoptotic wave is locally initiated in the axon by dual leucine zipper kinase (DLK). We found that mitochondrial fission and resultant cell death are entirely dependent on phosphorylation of dynamin related protein 1 (DRP1) downstream of DLK, revealing a new mechanism by which DLK can drive apoptosis. Importantly, we show that CRISPR mediated
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PMID36778383
PMCPMC9915495
OpenAlexW4319018793
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