Evidence map›Paper›PMID 42738830›Full record

ArticleCells2026

Sigma-1 Receptor Stimulation Rescues FTD/ALS Mutant TDP43-Induced Disruption of the VAPB-PTPIP51 ER-Mitochondria Tethering Proteins via Inhibition of GSK3β.

Kerry Blair, Philippe Gosset, Raquel Martinez-Serra, Gábor M Mórotz, Sandra M Martín-Guerrero, Patricia Gomez-Suaga, Joseph Atherton, Jacqueline C Mitchell, Wendy Noble, Christopher C J Miller and 1 more

Abstract read
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In one paragraph

Article in Cells, 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

11 authors.

Kerry BlairDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London WC2R 2LS, UK.ORCID 0000-0001-6358-3854
Philippe GossetDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London WC2R 2LS, UK.ORCID 0000-0002-9104-8688
Raquel Martinez-SerraDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London WC2R 2LS, UK.
Gábor M MórotzDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London WC2R 2LS, UK.ORCID 0000-0003-4223-7009
Sandra M Martín-GuerreroDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London WC2R 2LS, UK.ORCID 0000-0003-1489-4757
Patricia Gomez-SuagaDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London WC2R 2LS, UK.ORCID 0000-0002-2388-8327
Joseph AthertonRandall Centre for Cell and Molecular Biophysics, King's College London, London WC2R 2LS, UK.ORCID 0000-0002-6362-2347
Jacqueline C MitchellDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London WC2R 2LS, UK.ORCID 0000-0002-2677-398X
Wendy NobleDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London WC2R 2LS, UK.
Christopher C J MillerDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London WC2R 2LS, UK.
Andrea MarkovinovicDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London WC2R 2LS, UK.ORCID 0000-0003-1656-3150

Funding

Alzheimer's Research UK ARUK-DC2019-009Alzheimer's Research UK ARUK-PG2017B-3Alzheimer's Society AlzSoc-287Medical Research Council MR/R022666/1Medical Research Council MR/X021858/1
6 · The paper itself

Abstract

Signalling between the ER and mitochondria regulates a number of key cellular functions that are damaged in frontotemporal dementia and related amyotrophic lateral sclerosis (FTD/ALS). This signalling involves close physical contacts between the two organelles that are mediated by the VAPB-PTPIP51 ER-mitochondria "tethering" proteins. A number of studies have shown that mutant genes which cause familial FTD/ALS disrupt the VAPB-PTPIP51 tethers and that this involves activation of GSK3β. TDP43 is one such mutant and altered TDP43 metabolism is central to FTD/ALS pathogenesis. Loss of Sigma-1 receptor function is also seen in FTD/ALS and there is evidence that Sigma-1 receptor agonists can repair damaged ER-mitochondria signalling. However, the underlying mechanisms are not properly understood. In this study, we show that the reference Sigma-1 receptor agonist PRE-084 stimulates VAPB-PTPIP51 binding and rescues FTD/ALS mutant TDP43-induced disruption to the VAPB-PTPIP51 interaction and linked ER-mitochondria Ca

Indexed as

Amyotrophic Lateral SclerosisDNA-Binding ProteinsEndoplasmic ReticulumFrontotemporal DementiaGlycogen Synthase Kinase 3 betaMitochondriaMitochondrial ProteinsMutationReceptors, sigmaAnimalsCalciumHumansMitochondria Associated MembranesProtein BindingSigma-1 ReceptorCalciumDNA-Binding ProteinsGlycogen Synthase Kinase 3 betaGSK3B protein, humanMitochondrial ProteinsReceptors, sigmaSigma-1 ReceptorTARDBP protein, humanamyotrophic lateral sclerosisANAVEX2-73frontotemporal dementiaPRE-084PTPIP51Sigma-1 receptorTDP43VAPB

Identifiers

PMID42738830
PMCPMC13565437

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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.