Evidence map›Paper›PMID 41028791›Full record

ArticleScientific reports2025

Detecting MUNC18-1 related presynaptic dysfunction and rescue in human iPSC-derived neurons.

Manzhao Long, Nicholas B Gallo, Jennifer Zoll, Sharanya Unnikrishnan, Edward Guilmette, Davide Gianni, Sijia Wu, Christopher A Hinckley

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PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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.

Manzhao Long *Biogen, Cambridge, MA, USA.
Nicholas B GalloBiogen, Cambridge, MA, USA.
Jennifer Zoll *Biogen, Cambridge, MA, USA.
Sharanya Unnikrishnan *Biogen, Cambridge, MA, USA.
Edward Guilmette *Biogen, Cambridge, MA, USA.
Davide GianniBiogen, Cambridge, MA, USA.
Sijia WuBiogen, Cambridge, MA, USA.
Christopher A HinckleyBiogen, Cambridge, MA, USA. chris.hinckley@biogen.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Human induced pluripotent stem cell (hiPSC) derived neurons are powerful tools to model disease biology in the drug development space. Here we leveraged a spectrum of neurophysiological tools to characterize iPSC-derived NGN2 neurons. Specifically, we applied these technologies to detect phenotypes associated with presynaptic dysfunction and rescue in NGN2 neurons lacking a synaptic vesicle associated protein MUNC18-1, encoded by syntaxin binding protein 1 gene (STXBP1). STXBP1 homozygous knock out NGN2 neurons lacked miniature post synaptic currents and demonstrated disrupted network bursting as assayed with multielectrode array and calcium imaging. Furthermore, knock out neurons released less glutamate into culture media, consistent with a presynaptic deficit. These synaptic phenotypes were rescued by reconstitution of STXBP1 protein by AAV transduction in a dose-dependent manner. Our results identify a complementary suite of physiological methods suitable to examine the modulation of synaptic transmission in human neurons.

Indexed as

Induced Pluripotent Stem CellsMunc18 ProteinsNeuronsPresynaptic TerminalsCalciumCells, CulturedGlutamic AcidHumansSynaptic TransmissionCalciumGlutamic AcidMunc18 ProteinsSTXBP1 protein, human

Identifiers

PMID41028791
PMCPMC12484815

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Registered trials

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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.