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Rep"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The pathology of Huntington\u2019s 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\n                      <jats:italic>HTT<\/jats:italic>\n                      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 Ca\u00b2\u207a depletion triggers extracellular Ca\u00b2\u207a 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We 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\u00a0H-carbazol-1-amine hydrochloride (C\n                      <jats:sub>20<\/jats:sub>\n                      H\n                      <jats:sub>22<\/jats:sub>\n                      BrClN\n                      <jats:sub>2<\/jats:sub>\n                      ) and EVP4593, in premanifest HD fibroblasts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The 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\n                      <jats:sub>20<\/jats:sub>\n                      H\n                      <jats:sub>22<\/jats:sub>\n                      BrClN\n                      <jats:sub>2<\/jats:sub>\n                      and EVP4593 show potential for stabilizing SOCE in adult-onset HD. These findings suggest that dysregulated SOCE could be investigated as a peripheral target for studying pathological processes potentially associated with Huntington\u2019s disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s43440-025-00820-8","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T05:30:52Z","timestamp":1768887052000},"page":"568-581","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dysregulation of store-operated calcium entry in fibroblast lines from adult and juvenile-onset Huntington\u2019s disease patients"],"prefix":"10.1007","volume":"78","author":[{"given":"Samuel Oluwafemi","family":"Egbuwalo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7883-6989","authenticated-orcid":false,"given":"Ewelina","family":"Latoszek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8962-1975","authenticated-orcid":false,"given":"Hana","family":"Hans\u00edkov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0735-7155","authenticated-orcid":false,"given":"Ji\u0159\u00ed","family":"Klemp\u00ed\u0159","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0385-3071","authenticated-orcid":false,"given":"Al\u017ebeta","family":"M\u00fchlb\u00e4ck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3375-790X","authenticated-orcid":false,"given":"Georg Bernhard","family":"Landwehrmeyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6486-0657","authenticated-orcid":false,"given":"Jacek","family":"Ku\u017anicki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5419-1234","authenticated-orcid":false,"given":"Magdalena","family":"Czeredys","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"issue":"5","key":"820_CR1","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1016\/S0896-6273(02)00872-3","volume":"35","author":"CA Ross","year":"2002","unstructured":"Ross CA. 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All procedures involving human cells were conducted in accordance with institutional and national ethical guidelines, as well as the principles of the Declaration of Helsinki. Written informed consents were obtained from all donors or their legally authorized representatives before sample collection. Commercially available GM09197 and GM05539 fibroblast lines used in this study were obtained through secondary distribution with the approval of the Coriell Institute for Medical Research.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}