Evidence map›Paper›PMID 33515429›Full record

ReviewCNS drugs2021

Inhibitors of Src Family Kinases, Inducible Nitric Oxide Synthase, and NADPH Oxidase as Potential CNS Drug Targets for Neurological Diseases.

Meghan C Gage, Thimmasettappa Thippeswamy

Open access · greenAbstract readReview
In one paragraph

Review in CNS drugs, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

28 citing papers in PubMed, 47 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Neuroinflammation in Alzheimer disease.Nature reviews. Immunology · 2025
    Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Optogenetics in Alzheimer's Disease: Focus on Astrocytes.Antioxidants (Basel, Switzerland) · 2023
    Review
  16. Tanshinone-IIA mediated neuroprotection by modulating neuronal pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2023
    Review
  17. Article
  18. Article
  19. Review
  20. 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

2 authors at 1 institution in 1 country.

Meghan C GageIowa State University, Ames, Iowa, USA.
Thimmasettappa ThippeswamyIowa State University, Ames, Iowa, USA. tswamy@iastate.edu.ORCID http://orcid.org/0000-0002-9326-1896
Iowa State University · US

Funding

Saracatinib Mitigates OP nerve agent-induced Long-term NeurotoxicityR21NS110648 · NINDS · IOWA STATE UNIVERSITY · PI THIPPESWAMY, THIMMASETTAPPA · 2019 to 2020
$412k
Fyn Mediated Neuroinflammatory Signaling in Epileptogenesis and EpilepsyR21NS112779 · NINDS · IOWA STATE UNIVERSITY · PI THIPPESWAMY, THIMMASETTAPPA · 2020 to 2020
$407k
Toxin-specific and symptomatic drugs in combination with novel neuroprotectants effectively counteract DFP-induced long-term neurotoxicityR21NS099007 · NINDS · IOWA STATE UNIVERSITY · PI THIPPESWAMY, THIMMASETTAPPA · 2017 to 2018
$396k
NINDS NIH HHS R21 NS099007NINDS NIH HHS R21 NS110648NINDS NIH HHS R21 NS112779
6 · The paper itself

Abstract

Neurological diseases share common neuroinflammatory and oxidative stress pathways. Both phenotypic and molecular changes in microglia, astrocytes, and neurons contribute to the progression of disease and present potential targets for disease modification. Src family kinases (SFKs) are present in both neurons and glial cells and are upregulated following neurological insults in both human and animal models. In neurons, SFKs interact with post-synaptic protein domains to mediate hyperexcitability and neurotoxicity. SFKs are upstream of signaling cascades that lead to the modulation of neurotransmitter receptors and the transcription of pro-inflammatory cytokines as well as producers of free radicals through the activation of glia. Inducible nitric oxide synthase (iNOS/NOS-II) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2), the major mediators of reactive nitrogen/oxygen species (RNS/ROS) production in the brain, are also upregulated along with the pro-inflammatory cytokines following neurological insult and contribute to disease progression. Persistent neuronal hyperexcitability, RNS/ROS, and cytokines can exacerbate neurodegeneration, a common pathognomonic feature of the most prevalent neurological disorders such as Alzheimer's disease, Parkinson's disease, and epilepsy. Using a wide variety of preclinical disease models, inhibitors of the SFK-iNOS-NOX2 signaling axis have been tested to cure or modify disease progression. In this review, we discuss the SFK-iNOS-NOX2 signaling pathway and their inhibitors as potential CNS targets for major neurological diseases.

Indexed as

Drug DevelopmentAnimalsCentral Nervous System DiseasesDisease ProgressionEnzyme InhibitorsHumansNADPH OxidasesNitric Oxide Synthase Type IISignal Transductionsrc-Family KinasesEnzyme InhibitorsNADPH OxidasesNitric Oxide Synthase Type IINOS2 protein, humansrc-Family Kinases

Identifiers

PMID33515429
PMCPMC7893831
OpenAlexW3125910123

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.