Ischemic axonal injury up-regulates MARK4 in cortical neurons and primes tau phosphorylation and aggregation
Posted on 2019-08-21 - 04:29
Abstract Ischemic injury to white matter tracts is increasingly recognized to play a key role in age-related cognitive decline, vascular dementia, and Alzheimerâs disease. Knowledge of the effects of ischemic axonal injury on cortical neurons is limited yet critical to identifying molecular pathways that link neurodegeneration and ischemia. Using a mouse model of subcortical white matter ischemic injury coupled with retrograde neuronal tracing, we employed magnetic affinity cell sorting with fluorescence-activated cell sorting to capture layer-specific cortical neurons and performed RNA-sequencing. With this approach, we identified a role for microtubule reorganization within stroke-injured neurons acting through the regulation of tau. We find that subcortical stroke-injured Layer 5 cortical neurons up-regulate the microtubule affinity-regulating kinase, Mark4, in response to axonal injury. Stroke-induced up-regulation of Mark4 is associated with selective remodeling of the apical dendrite after stroke and the phosphorylation of tau in vivo. In a cell-based tau biosensor assay, Mark4 promotes the aggregation of human tau in vitro. Increased expression of Mark4 after ischemic axonal injury in deep layer cortical neurons provides new evidence for synergism between axonal and neurodegenerative pathologies by priming of tau phosphorylation and aggregation.
CITE THIS COLLECTION
DataCite
3 Biotech
3D Printing in Medicine
3D Research
3D-Printed Materials and Systems
4OR
AAPG Bulletin
AAPS Open
AAPS PharmSciTech
Abhandlungen aus dem Mathematischen Seminar der Universität Hamburg
ABI Technik (German)
Academic Medicine
Academic Pediatrics
Academic Psychiatry
Academic Questions
Academy of Management Discoveries
Academy of Management Journal
Academy of Management Learning and Education
Academy of Management Perspectives
Academy of Management Proceedings
Academy of Management Review
Hayden, Eric; Putman, Jennifer; Nunez, Stefanie; Shin, Woo; Oberoi, Mandavi; Charreton, Malena; et al. (2019). Ischemic axonal injury up-regulates MARK4 in cortical neurons and primes tau phosphorylation and aggregation. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.4638086.v1
or
Select your citation style and then place your mouse over the citation text to select it.
SHARE
Usage metrics
Read the peer-reviewed publication
AUTHORS (14)
EH
Eric Hayden
JP
Jennifer Putman
SN
Stefanie Nunez
WS
Woo Shin
MO
Mandavi Oberoi
MC
Malena Charreton
SD
Suman Dutta
ZL
Zizheng Li
YK
Yutaro Komuro
MJ
Mary Joy
GB
Gal Bitan
AM
Allan MacKenzie-Graham
LJ
Lin Jiang
JH
Jason Hinman