{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T09:31:44Z","timestamp":1776331904412,"version":"3.50.1"},"reference-count":36,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T00:00:00Z","timestamp":1762560000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007065","name":"University of Salerno","doi-asserted-by":"publisher","award":["ORSA231580"],"award-info":[{"award-number":["ORSA231580"]}],"id":[{"id":"10.13039\/501100007065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Protein misfolding diseases are characterized by structurally abnormal proteins that lose their functionality, resulting in cellular and tissue dysfunction. Neurodegenerative diseases, including Parkinson\u2019s disease, Alzheimer\u2019s disease and Huntington\u2019s disease, share a common etiopathogenesis characterize by the accumulation of misfolded proteins. These proteins autonomously aggregate within neuronal cells, triggering inflammation and cell death. The accumulation of misfolded proteins triggers endoplasmic reticulum (ER) stress, leading to alter Ca2+ homeostasis. This prolonged stress condition induces the cleavage of procaspase 4 which is resident in ER and activates NF-kB pathway activation, leading to inflammatory responses and cell death. In this study, the efficacy of the drug Vx-445 (Elexacaftor), used in the pharmacological treatment of cystic fibrosis, was assessed in human adenocarcinomic basal alveolar epithelial (A549) and neuronal (SH-SY5Y) cell lines, where ER stress was induced by Thapsigargin. The aim was to assess whether the corrector was able to reduce ER stress by restoring cellular homeostasis and, probably, the proper folding of misfolded proteins and reducing the inflammatory response triggered by these events. Therefore, protein levels of IkB\u03b1, p-STAT 3 and COXII were analyzed by flow cytofluorimetry, while Ca2+ content was measured by spectrofluorimetry. The results obtained suggest a significant effect of Vx-445 in restoring cellular homeostasis, leading to reduced expression of inflammation-related proteins, such as IL-6, tested by ELISA. Although preliminary, these results encourage further studies to explore the potential repurpose of Vx-445 as a therapeutic candidate for conditions involving ER stress and chronic inflammatory diseases associated with protein misfolding, beyond its current use in cystic fibrosis.<\/jats:p>","DOI":"10.3390\/ijms262210846","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T08:57:55Z","timestamp":1762765075000},"page":"10846","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["New Role of Protein Misfolding Corrector in the ER Stress-Inflammation Axis: Possible Therapeutic Indication in Neuronal and Epithelial Tumor Cells"],"prefix":"10.3390","volume":"26","author":[{"given":"Michela","family":"Pecoraro","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 84084 Fisciano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adele","family":"Serra","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 84084 Fisciano, Italy"},{"name":"Ph.D. Program in Drug Discovery and Development, University of Salerno, 84084 Fisciano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7162-0520","authenticated-orcid":false,"given":"Maria Julia","family":"Lamberti","sequence":"additional","affiliation":[{"name":"Instituto de Biotecnolog\u00eda Ambiental y Salud (INBIAS UNRC CONICET)-UNRC, R\u00edo Cuarto 5800, Argentina"},{"name":"Departamento de Biolog\u00eda Molecular, Facultad de Ciencias Exactas, F\u00edsico-Qu\u00edmicas y Naturales, Universidad Nacional de R\u00edo Cuarto, R\u00edo Cuarto 5800, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Pascale","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 84084 Fisciano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7412-7918","authenticated-orcid":false,"given":"Silvia","family":"Franceschelli","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 84084 Fisciano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zimmermann, J.S.M., Linxweiler, J., Radosa, J.C., Linxweiler, M., and Zimmermann, R. 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