Evidence map›Paper›PMID 42412610›Full record

ArticleCell reports2026

Striatal neuron dysfunction in C9ORF72-FTD/ALS is driven by AIS and potassium channel dysregulation.

Iris-Stefania Pasniceanu, Manpreet S Atwal, Cleide Dos Santos Souza, Tobias Moll, Marianne King, Connie Treanor, Daniel Cabezas de la Fuente, Ryan J H West, Laura Ferraiuolo, Matthew R Livesey

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Iris-Stefania PasniceanuSheffield Institute for Translational Neuroscience, Division of Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK; The Neuroscience Institute, University of Sheffield, Sheffield S10 2HQ, UK.
Manpreet S AtwalSheffield Institute for Translational Neuroscience, Division of Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK; The Neuroscience Institute, University of Sheffield, Sheffield S10 2HQ, UK.
Cleide Dos Santos SouzaSheffield Institute for Translational Neuroscience, Division of Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK; The Neuroscience Institute, University of Sheffield, Sheffield S10 2HQ, UK.
Tobias MollSheffield Institute for Translational Neuroscience, Division of Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK; The Neuroscience Institute, University of Sheffield, Sheffield S10 2HQ, UK.
Marianne KingSheffield Institute for Translational Neuroscience, Division of Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK; The Neuroscience Institute, University of Sheffield, Sheffield S10 2HQ, UK.
Connie TreanorSheffield Institute for Translational Neuroscience, Division of Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK; The Neuroscience Institute, University of Sheffield, Sheffield S10 2HQ, UK.
Daniel Cabezas de la FuenteSheffield Institute for Translational Neuroscience, Division of Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK; The Neuroscience Institute, University of Sheffield, Sheffield S10 2HQ, UK.
Ryan J H WestSheffield Institute for Translational Neuroscience, Division of Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK; The Neuroscience Institute, University of Sheffield, Sheffield S10 2HQ, UK.
Laura FerraiuoloSheffield Institute for Translational Neuroscience, Division of Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK; The Neuroscience Institute, University of Sheffield, Sheffield S10 2HQ, UK.
Matthew R LiveseySheffield Institute for Translational Neuroscience, Division of Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK; The Neuroscience Institute, University of Sheffield, Sheffield S10 2HQ, UK. Electronic address: m.r.livesey@sheffield.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) form a neurodegenerative spectrum characterized by progressive cognitive, behavioral, and motor decline, yet the contribution of the striatum to disease pathophysiology remains poorly understood. Here, we generate inhibitory striatal medium spiny neurons (MSNs) from human induced pluripotent stem cells carrying the C9ORF72 repeat expansion, the most common genetic cause of FTD/ALS, and compare them with isogenic-corrected, control, and patient-derived motor neurons. Using whole-cell electrophysiology, pharmacological manipulation, and high-resolution imaging, we identify a vulnerability of C9ORF72 MSNs to develop intrinsic hypoexcitability with linked synaptic dysfunction. These abnormalities are associated with axon initial segment shortening and altered voltage-gated potassium channel function relative to control and isogenic-corrected neurons. Pharmacological modulation partially restores action potential waveform properties, indicating that key electrophysiological abnormalities are reversible. These findings identify the striatum as a critical site of dysfunction in FTD/ALS and highlight striatal excitability as a potential therapeutic target.

Indexed as

Amyotrophic Lateral SclerosisC9orf72 ProteinCorpus StriatumFrontotemporal DementiaNeuronsPotassium ChannelsAction PotentialsAxon Initial SegmentHumansInduced Pluripotent Stem CellsMedium Spiny NeuronsC9orf72 ProteinC9orf72 protein, humanPotassium ChannelsALSC9ORF72CP: neuroscienceelectrophysiologyexcitabilityFTDinhibitoryneuronstriatalsynaptic

Identifiers

PMID42412610
PMCPMC13415681

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.