Remyelination protects neurons from DLK-mediated neurodegeneration

Greg J. Duncan (), Sam D. Ingram, Katie Emberley, Jo Hill, Christian Cordano, Ahmed Abdelhak, Michael McCane, Jennifer E. Jenks, Nora Jabassini, Kirtana Ananth, Skylar J. Ferrara, Brittany Stedelin, Benjamin Sivyer, Sue A. Aicher, Thomas S. Scanlan, Trent A. Watkins, Anusha Mishra, Jonathan W. Nelson, Ari J. Green and Ben Emery ()
Additional contact information
Greg J. Duncan: Oregon Health & Science University
Sam D. Ingram: Oregon Health & Science University
Katie Emberley: Oregon Health & Science University
Jo Hill: Oregon Health & Science University
Christian Cordano: University of California San Francisco
Ahmed Abdelhak: University of California San Francisco
Michael McCane: Oregon Health & Science University
Jennifer E. Jenks: Oregon Health & Science University
Nora Jabassini: University of California San Francisco
Kirtana Ananth: University of California San Francisco
Skylar J. Ferrara: Oregon Health & Science University
Brittany Stedelin: Oregon Health & Science University
Benjamin Sivyer: Oregon Health & Science University
Sue A. Aicher: Oregon Health & Science University
Thomas S. Scanlan: Oregon Health & Science University
Trent A. Watkins: University of California San Francisco
Anusha Mishra: Oregon Health & Science University
Jonathan W. Nelson: Oregon Health & Science University
Ari J. Green: University of California San Francisco
Ben Emery: Oregon Health & Science University

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract Chronic demyelination and oligodendrocyte loss deprive neurons of crucial support. It is the degeneration of neurons and their connections that drives progressive disability in demyelinating disease. However, whether chronic demyelination triggers neurodegeneration and how it may do so remain unclear. We characterize two genetic mouse models of inducible demyelination, one distinguished by effective remyelination and the other by remyelination failure and chronic demyelination. While both demyelinating lines feature axonal damage, mice with blocked remyelination have elevated neuronal apoptosis and altered microglial inflammation, whereas mice with efficient remyelination do not feature neuronal apoptosis and have improved functional recovery. Remyelination incapable mice show increased activation of kinases downstream of dual leucine zipper kinase (DLK) and phosphorylation of c-Jun in neuronal nuclei. Pharmacological inhibition or genetic disruption of DLK block c-Jun phosphorylation and the apoptosis of demyelinated neurons. Together, we demonstrate that remyelination is associated with neuroprotection and identify DLK inhibition as protective strategy for chronically demyelinated neurons.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-024-53429-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53429-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-53429-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().