Evidence map›Paper›PMID 29944965›Full record

ArticleNeurobiology of disease2019

CK2 inhibition confers functional protection to young and aging axons against ischemia by differentially regulating the CDK5 and AKT signaling pathways.

Chinthasagar Bastian, John Quinn, Ajai Tripathi, Danielle Aquila, Andrew McCray, Ranjan Dutta, Selva Baltan, Sylvain Brunet

Open access · greenAbstract read
In one paragraph

Article in Neurobiology of disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.2field-weighted citation impact, top 21% of its field
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

15 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Casein Kinase 2 Signaling in White Matter Stroke.Frontiers in molecular biosciences · 2022
    Review
  8. Article
  9. Review
  10. New insights into targeting mitochondria in ischemic injury.Apoptosis : an international journal on programmed cell death · 2021
    Review
  11. Article
  12. Post-stroke remodeling processes in animal models and humans.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020
    Review
  13. Ex Vivo Studies of Optic Nerve Axon Electrophysiology.Methods in molecular biology (Clifton, N.J.) · 2020
    Article
  14. Article
  15. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Chinthasagar BastianDepartments of Neurosciences, Cleveland Clinic, Cleveland, OH 44195, United States of America.
John QuinnDepartments of Neurosciences, Cleveland Clinic, Cleveland, OH 44195, United States of America.
Ajai TripathiDepartments of Neurosciences, Cleveland Clinic, Cleveland, OH 44195, United States of America.
Danielle AquilaDepartments of Neurosciences, Cleveland Clinic, Cleveland, OH 44195, United States of America.
Andrew McCrayDepartments of Neurosciences, Cleveland Clinic, Cleveland, OH 44195, United States of America.
Ranjan DuttaDepartments of Neurosciences, Cleveland Clinic, Cleveland, OH 44195, United States of America.
Selva BaltanDepartments of Neurosciences, Cleveland Clinic, Cleveland, OH 44195, United States of America. Electronic address: baltans@ccf.org.
Sylvain BrunetDepartments of Neurosciences, Cleveland Clinic, Cleveland, OH 44195, United States of America. Electronic address: brunets@ccf.org.
Cleveland Clinic · US

Funding

Vulnerability of Aging White Matter to IschemiaR01AG033720 · NIA · UNIVERSITY OF WASHINGTON · PI BALTAN, SELVA · 2010 to 2021
$2.7M
MicroRNAs as critical regulators of remyelination in Multiple SclerosisR01NS096148 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI DUTTA, RANJAN · 2016 to 2020
$1.7M
Casein kinase 2 signaling in axonal injuryR21NS094881 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI BALTAN, SELVA · 2016 to 2017
$436k
Vulnerability of Aging White Matter to IschemiaR56AG033720 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI BALTAN, SELVA · 2016 to 2016
$396k
NIA NIH HHS R01 AG033720NIA NIH HHS R56 AG033720NINDS NIH HHS R01 NS096148NINDS NIH HHS R21 NS094881
6 · The paper itself

Abstract

White matter (WM) is injured in most strokes, which contributes to functional deficits during recovery. Casein kinase 2 (CK2) is a protein kinase that is expressed in brain, including WM. To assess the impact of CK2 inhibition on axon recovery following oxygen glucose deprivation (OGD), mouse optic nerves (MONs), which are pure WM tracts, were subjected to OGD with or without the selective CK2 inhibitor CX-4945. CX-4945 application preserved axon function during OGD and promoted axon function recovery when applied before or after OGD. This protective effect of CK2 inhibition correlated with preservation of oligodendrocytes and conservation of axon structure and axonal mitochondria. To investigate the pertinent downstream signaling pathways, siRNA targeting the CK2α subunit identified CDK5 and AKT as downstream molecules. Consequently, MK-2206 and roscovitine, which are selective AKT and CDK5 inhibitors, respectively, protected young and aging WM function only when applied before OGD. However, a novel pan-AKT allosteric inhibitor, ARQ-092, which targets both the inactive and active conformations of AKT, conferred protection to young and aging axons when applied before or after OGD. These results suggest that AKT and CDK5 signaling contribute to the WM functional protection conferred by CK2 inhibition during ischemia, while inhibition of activated AKT signaling plays the primary role in post-ischemic protection conferred by CK2 inhibition in WM independent of age. CK2 inhibitors are currently being used in clinical trials for cancer patients; therefore, our results will provide rationale for repurposing these drugs as therapeutic options for stroke patients by adding novel targets.

Indexed as

AgingAnimalsAxonsBrain IschemiaCasein Kinase IICyclin-Dependent Kinase 5MaleMiceMice, Inbred C57BLProto-Oncogene Proteins c-aktSignal TransductionCasein Kinase IICdk5 protein, mouseCyclin-Dependent Kinase 5Proto-Oncogene Proteins c-aktAgingMyelinOligodendrocyteStrokeWhite matter

Identifiers

PMID29944965
PMCPMC9084539
OpenAlexW2810563348

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.