Evidence map›Paper›PMID 25448156›Full record

ArticleExperimental neurology2015

Fluoxetine is neuroprotective in slow-channel congenital myasthenic syndrome.

Haipeng Zhu, Gary E Grajales-Reyes, Vivianette Alicea-Vázquez, Jose G Grajales-Reyes, KaReisha Robinson, Peter Pytel, Carlos A Báez-Pagán, Jose A Lasalde-Dominicci, Christopher M Gomez

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Experimental neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
0.6field-weighted citation impact, top 30% 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

5 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.

  1. Pooled it
  2. Reduction of the CaFrontiers in cellular neuroscience · 2025
    Review
  3. Article
  4. Review
  5. Treating pediatric neuromuscular disorders: The future is now.American journal of medical genetics. Part A · 2018
    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

9 authors at 3 institutions in 2 countries.

Haipeng ZhuDepartment of Neurology, The University of Chicago, Chicago, IL, USA.
Gary E Grajales-ReyesSchool of Medicine, Washington University, St. Louis, St. Louis, MO, USA.
Vivianette Alicea-VázquezDepartment of Biology, The University of Puerto Rico, San Juan, Puerto Rico, USA.
Jose G Grajales-ReyesSchool of Medicine, Washington University, St. Louis, St. Louis, MO, USA.
KaReisha RobinsonDepartment of Neurology, The University of Chicago, Chicago, IL, USA.
Peter PytelDepartment of Pathology, The University of Chicago, Chicago, IL, USA.
Carlos A Báez-PagánDepartment of Biology, The University of Puerto Rico, San Juan, Puerto Rico, USA.
Jose A Lasalde-DominicciDepartment of Biology, The University of Puerto Rico, San Juan, Puerto Rico, USA.
Christopher M GomezDepartment of Neurology, The University of Chicago, Chicago, IL, USA. Electronic address: gomez001@uchicago.edu.
University of Chicago · USUniversity of Puerto Rico System · PRWashington University in St. Louis · US

Funding

The Role of Sensory Input to Mammalian Locomotion After the Loss of supraspinal.P20GM103642 · NIGMS · UNIVERSITY OF PUERTO RICO MED SCIENCES · PI LASALDE-DOMINICCI, JOSE ANTONIO · 2013 to 2023
$20.6M
Re-Engineering Translational Research at the University of ChicagoUL1TR000430 · NCATS · UNIVERSITY OF CHICAGO · PI SOLWAY, JULIAN · 2012 to 2016
$20.2M
ACETYLCHOLINE RECEPTOR GENES IN SLOW CHANNEL SYNDROMER01NS033202 · NINDS · UNIVERSITY OF MINNESOTA TWIN CITIES · PI GOMEZ, CHRISTOPHER MANUEL · 1995 to 2014
$4.5M
NCATS NIH HHS UL1 TR000430NIGMS NIH HHS P20 GM103642NINDS NIH HHS R01 NS033202NINDS NIH HHS R01 NS33202PHS HHS NIGMS 1P20GM103642
6 · The paper itself

Abstract

The slow-channel congenital myasthenic syndrome (SCS) is an inherited neurodegenerative disease that caused mutations in the acetylcholine receptor (AChR) affecting neuromuscular transmission. Leaky AChRs lead to Ca(2+) overload and degeneration of the neuromuscular junction (NMJ) attributed to activation of cysteine proteases and apoptotic changes of synaptic nuclei. Here we use transgenic mouse models expressing two different mutations found in SCS to demonstrate that inhibition of prolonged opening of mutant AChRs using fluoxetine not only improves motor performance and neuromuscular transmission but also prevents Ca(2+) overload, the activation of cysteine proteases, calpain, caspase-3 and 9 at endplates, and as a consequence, reduces subsynaptic DNA damage at endplates, suggesting a long term benefit to therapy. These studies suggest that prolonged treatment of SCS patients with open ion channel blockers that preferentially block mutant AChRs is neuroprotective.

Indexed as

AnimalsDisease Models, AnimalFluoxetineMaleMiceMice, TransgenicMotor ActivityMyasthenic Syndromes, CongenitalNeuromuscular JunctionNeuroprotective AgentsPatch-Clamp TechniquesRecovery of FunctionFluoxetineNeuroprotective AgentsAcetylcholine receptorCa2+ overloadFluoxetineIon channel blockersMutationNeurodegenerative diseaseNeuromuscular junctionNeuromuscular transmissionNeuroprotectiveSlow-channel congenital myasthenic syndromeSubsynaptic DNA damage

Identifiers

PMID25448156
PMCPMC4430442
OpenAlexW2076855700

What OpenQuestion holds

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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.