Targeted disruption of dual leucine zipper kinase and leucine zipper kinase promotes neuronal survival in a model of diffuse traumatic brain injury
Abstract
Traumatic brain injury (TBI) is a major cause of CNS neurodegeneration and has no disease-altering therapies. It is commonly associated with a specific type of biomechanical disruption of the axon called traumatic axonal injury (TAI), which often leads to axonal and sometimes perikaryal degeneration of CNS neurons. We have previously used genome-scale, arrayed RNA interference-based screens in primary mouse retinal ganglion cells (RGCs) to identify a pair of related kinases, dual leucine zipper kinase (DLK) and leucine zipper kinase (LZK) that are key mediators of cell death in response to simple axotomy. Moreover, we showed that DLK and LZK are the major upstream triggers for JUN N-terminal kinase (JNK) signaling following total axonal transection. However, the degree to which DLK/LZK are involved in TAI/TBI is unknown.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 27, 2019
- Source ID
- 10.1186/s13024-019-0345-1
Entities
People
- Amit K. Patel
- Athanasios S. Alexandris
- Byung-jin Kim
- Derek S Welsbie
- Donald J. Zack
- Jiwon Ryu
- Leyan Xu
- Mohamed Lehar
- Nicholas Stewart
- Nikolaos K. Ziogas
- Vassilis E. Koliatsos
- Yusong Ge
Organizations
- BrightFocus Foundation
- E. Matilda Ziegler Foundation for the Blind
- National Eye Institute
- Research to Prevent Blindness
- United States Department of Defense