Evidence map›Paper›PMID 26576229›Full record

ReviewOxidative medicine and cellular longevity2015

Mechanisms of Neuronal Protection against Excitotoxicity, Endoplasmic Reticulum Stress, and Mitochondrial Dysfunction in Stroke and Neurodegenerative Diseases.

Howard Prentice, Jigar Pravinchandra Modi, Jang-Yen Wu

Open access · hybridAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Oxidative medicine and cellular longevity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
122citing papers in PubMed, 1 pooled it
10.2field-weighted citation impact, top 1% 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

122 citing papers in PubMed, 1 synthesis or guideline pooled it, 248 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Review
  6. Article
  7. Resting CaCellular and molecular life sciences : CMLS · 2025
    Article
  8. Article
  9. Therapeutic effects ofIBRO neuroscience reports · 2025
    Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Review

62 more citing papers are in PubMed but not listed here.

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

3 authors at 1 institution in 2 countries.

Howard PrenticeCollege of Medicine, Florida Atlantic University, Boca Raton, FL 33431, USA ; Program in Integrative Biology, Florida Atlantic University, Boca Raton, FL 33431, USA ; Center for Complex Systems and Brain Sciences, Florida Atlantic University, Boca Raton, FL 33431, USA.
Jigar Pravinchandra ModiCollege of Medicine, Florida Atlantic University, Boca Raton, FL 33431, USA ; Center for Complex Systems and Brain Sciences, Florida Atlantic University, Boca Raton, FL 33431, USA.
Jang-Yen WuCollege of Medicine, Florida Atlantic University, Boca Raton, FL 33431, USA ; Program in Integrative Biology, Florida Atlantic University, Boca Raton, FL 33431, USA ; Center for Complex Systems and Brain Sciences, Florida Atlantic University, Boca Raton, FL 33431, USA ; China Medical University Hospital, Taichung, Taiwan.
Florida Atlantic University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In stroke and neurodegenerative disease, neuronal excitotoxicity, caused by increased extracellular glutamate levels, is known to result in calcium overload and mitochondrial dysfunction. Mitochondrial deficits may involve a deficiency in energy supply as well as generation of high levels of oxidants which are key contributors to neuronal cell death through necrotic and apoptotic mechanisms. Excessive glutamate receptor stimulation also results in increased nitric oxide generation which can be detrimental to cells as nitric oxide interacts with superoxide to form the toxic molecule peroxynitrite. High level oxidant production elicits neuronal apoptosis through the actions of proapoptotic Bcl-2 family members resulting in mitochondrial permeability transition pore opening. In addition to apoptotic responses to severe stress, accumulation of misfolded proteins and high levels of oxidants can elicit endoplasmic reticulum (ER) stress pathways which may also contribute to induction of apoptosis. Two categories of therapeutics are discussed that impact major pro-death events that include induction of oxidants, calcium overload, and ER stress. The first category of therapeutic agent includes the amino acid taurine which prevents calcium overload and is also capable of preventing ER stress by inhibiting specific ER stress pathways. The second category involves N-methyl-D-aspartate receptor (NMDA receptor) partial antagonists illustrated by S-Methyl-N, N-diethyldithiocarbamate sulfoxide (DETC-MeSO), and memantine. DETC-MeSO is protective through preventing excitotoxicity and calcium overload and by blocking specific ER stress pathways. Another NMDA receptor partial antagonist is memantine which prevents excessive glutamate excitation but also remarkably allows maintenance of physiological neurotransmission. Targeting of these major sites of neuronal damage using pharmacological agents is discussed in terms of potential therapeutic approaches for neurological disorders.

Indexed as

AnimalsDitiocarbEndoplasmic Reticulum StressHumansMitochondriaNeurodegenerative DiseasesNeurotoxinsReceptors, N-Methyl-D-AspartateSignal TransductionStrokeDitiocarbNeurotoxinsReceptors, N-Methyl-D-AspartateS-methyl N,N-diethylthiolcarbamate sulfoxide

Identifiers

PMID26576229
PMCPMC4630664
OpenAlexW1881066497

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.