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Lookup NU author(s): Dr Ella Dennis, Professor Michael Briggs
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2023 by the authors.The intracellular retention of mutant cartilage matrix proteins and pathological endoplasmic reticulum (ER) stress disrupts ossification and has been identified as a shared disease mechanism in a range of skeletal dysplasias including short limbed-dwarfism, multiple epiphyseal dysplasia type 5 (EDM5). Although targeting ER stress is an attractive avenue for treatment and has proven successful in the treatment of a related skeletal dysplasia, to date no drugs have proven successful in reducing ER stress in EDM5 caused by the retention of mutant matrilin-3. Our exciting findings show that by using our established luciferase ER stress screening assay, we can identify a “natural” chemical, curcumin, which is able to reduce pathological ER stress in a cell model of EDM5 by promoting the proteasomal degradation mutant matrilin-3. Therefore, this is an important in vitro study in which we describe, for the first time, the success of a naturally occurring chemical as a potential treatment for this currently incurable rare skeletal disease. As studies show that curcumin can be used as a potential treatment for range of diseases in vitro, current research is focused on developing novel delivery strategies to enhance its bioavailability. This is an important and exciting area of research that will have significant clinical impact on a range of human diseases including the rare skeletal disease, EDM5.
Author(s): Dennis EP, Watson RN, McPate F, Briggs MD
Publication type: Article
Publication status: Published
Journal: International Journal of Molecular Sciences
Year: 2023
Volume: 24
Issue: 2
Online publication date: 12/01/2023
Acceptance date: 09/01/2023
Date deposited: 07/02/2023
ISSN (print): 1661-6596
ISSN (electronic): 1422-0067
Publisher: MDPI
URL: https://doi.org/10.3390/ijms24021496
DOI: 10.3390/ijms24021496
PubMed id: 36675026
Notes: This article belongs to the Special Issue Bone Ontogeny, Embryology, and Homeostasis 2.0
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