Evidence map›Paper›PMID 41557250›Full record

ArticlePharmacological reports : PR2026

Dysregulation of store-operated calcium entry in fibroblast lines from adult and juvenile-onset Huntington's disease patients.

Samuel Oluwafemi Egbuwalo, Ewelina Latoszek, Hana Hansíková, Jiří Klempíř, Alžbeta Mühlbäck, Georg Bernhard Landwehrmeyer, Jacek Kuźnicki, Magdalena Czeredys

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

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Samuel Oluwafemi Egbuwalo *Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology in Warsaw, Warsaw, Poland.
Ewelina Latoszek *Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology in Warsaw, Warsaw, Poland.ORCID http://orcid.org/0000-0002-7883-6989
Hana HansíkováLaboratory for Study of Mitochondrial Disorders, Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.ORCID http://orcid.org/0000-0002-8962-1975
Jiří KlempířDepartment of Neurology, Center of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.ORCID http://orcid.org/0000-0002-0735-7155
Alžbeta MühlbäckIsar-Amper-Klinikum, Huntington-Zentrum-Süd, Klinik Taufkirchen, Taufkirchen, Germany.ORCID http://orcid.org/0000-0002-0385-3071
Georg Bernhard LandwehrmeyerDepartment of Neurology, Ulm University, Ulm, Germany.ORCID http://orcid.org/0000-0003-3375-790X
Jacek KuźnickiLaboratory of Neurodegeneration, International Institute of Molecular and Cell Biology in Warsaw, Warsaw, Poland.ORCID http://orcid.org/0000-0001-6486-0657
Magdalena CzeredysDepartment of Stem Cell Bioengineering, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawińskiego 5, Warsaw, 02-106, Poland. mczeredys@imdik.pan.pl.ORCID http://orcid.org/0000-0001-5419-1234

Funding

Ministry of Health of the Czech Republic MZ CR AZV-NU20-04-00136National Science Center in Poland "Opus" grant no. 2019/33/B/NZ3/02889
6 · The paper itself

Abstract

backgroundThe pathology of Huntington's disease (HD) is marked by the aggregation of mutant huntingtin protein (mHTT), which results from expanded polyglutamine (polyQ) residues encoded by CAG repeats in the HTT gene. These repeats are differentially elongated in adult- and juvenile-onset HD. In striatal neurons, the mHTT disrupts cellular mechanisms such as store-operated calcium entry (SOCE), a process in which endoplasmic reticulum Ca²⁺ depletion triggers extracellular Ca²⁺ influx; however, this process can also be affected in peripheral cells. The aim of this study was to evaluate SOCE in fibroblasts derived from both HD onset patients and age-related controls.

methodsWe conducted SOCE analysis in dermal fibroblasts from 12 HD patients (including adult- and juvenile-onset subtypes) and age-related healthy controls using Fura-2 AM ratiometric imaging paired with EGTA-based extracellular calcium chelation protocols. To evaluate SOCE response, we administered two SOC channel inhibitors, 6-bromo-N-(2-phenylethyl)-2,3,4,9-tetrahydro-1 H-carbazol-1-amine hydrochloride (C

resultsIn healthy human fibroblast lines, a decline in SOCE was observed between juvenile and adult individuals. In fibroblast lines from adult-onset HD patients (premanifest, early manifest, and manifest stages), we observed increased SOC channel activity. Conversely, juvenile-onset HD fibroblast lines exhibited reduced SOC channel activity compared to controls. Notably, SOCE dysregulation was independent of CAG repeat length in HD lines. Both SOC channel inhibitors attenuated SOCE in adult-onset HD lines.

conclusionThe mHTT upregulates SOCE in adult-onset HD fibroblasts and downregulates it in juvenile-onset HD fibroblast lines; however, SOCE levels do not correlate with the length of CAG repeats encoding mHTT. Despite opposing trends compared to age-related controls, similar levels of SOCE in both HD-onset fibroblasts were detected. Both C

Indexed as

CalciumCalcium ChannelsFibroblastsHuntington DiseaseAdolescentAdultAge of OnsetCell LineFemaleHumansHuntingtin ProteinMaleMiddle AgedYoung AdultCalciumCalcium ChannelsHTT protein, humanHuntingtin ProteinFibroblastsHuntingtinHuntington’s diseaseSOCE

Identifiers

PMID41557250
PMCPMC12975840

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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 Socratic graph.