The celecoxib derivatives AR-12 and AR-14 induce autophagy and clear prion-infected cells from prions
| العنوان: | The celecoxib derivatives AR-12 and AR-14 induce autophagy and clear prion-infected cells from prions |
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| المؤلفون: | Li Lu, Dalia H. A. Abdelaziz, Basant Abdulrahman, Alexander Zukiwski, Hermann M. Schätzl, Sabine Gilch, Simrika Thapa, Stefan Proniuk, Shubha Jain |
| المصدر: | Scientific Reports Scientific Reports, Vol 7, Iss 1, Pp 1-12 (2017) |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Gene isoform, PrPSc Proteins, animal diseases, lcsh:Medicine, Stimulation, Article, Pathogenesis, 03 medical and health sciences, Mice, In vivo, Cell Line, Tumor, Autophagy, Animals, lcsh:Science, Neurons, Sulfonamides, Multidisciplinary, Chemistry, lcsh:R, In vitro, 3. Good health, Cell biology, nervous system diseases, 030104 developmental biology, Cell culture, Celecoxib, Pyrazoles, Protein folding, lcsh:Q |
| الوصف: | Prion diseases are fatal infectious neurodegenerative disorders that affect both humans and animals. The autocatalytic conversion of the cellular prion protein (PrPC) into the pathologic isoform PrPSc is a key feature in prion pathogenesis. AR-12 is an IND-approved derivative of celecoxib that demonstrated preclinical activity against several microbial diseases. Recently, AR-12 has been shown to facilitate clearance of misfolded proteins. The latter proposes AR-12 to be a potential therapeutic agent for neurodegenerative disorders. In this study, we investigated the role of AR-12 and its derivatives in controlling prion infection. We tested AR-12 in prion infected neuronal and non-neuronal cell lines. Immunoblotting and confocal microscopy results showed that AR-12 and its analogue AR-14 reduced PrPSc levels after only 72 hours of treatment. Furthermore, infected cells were cured of PrPSc after exposure of AR-12 or AR-14 for only two weeks. We partially attribute the influence of the AR compounds on prion propagation to autophagy stimulation, in line with our previous findings that drug-induced stimulation of autophagy has anti-prion effects in vitro and in vivo. Taken together, this study demonstrates that AR-12 and the AR-14 analogue are potential new therapeutic agents for prion diseases and possibly protein misfolding disorders involving prion-like mechanisms. |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c6ddae9b6f9daf9789254e13b49e292aTest https://pubmed.ncbi.nlm.nih.gov/29242534Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c6ddae9b6f9daf9789254e13b49e292a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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