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Ding, Mingxuan; Teruya, Kenta; Zhang, Weiguanliu; Lee, Hae Weon; Yuan, Jue; Oguma, Ayumi; Foutz, Aaron; Camacho, Manuel V.; Mitchell, Marcus; Greenlee, Justin J.; Kong, Qingzhong; Doh-ura, Katsumi; Cui, Li; Zou, Wen-Quan
Molecular neurobiology, 09/2021, Letnik: 58, Številka: 9Journal Article
Previous studies have revealed that the infectious scrapie isoform of prion protein (PrP Sc ) harbored in the skin tissue of patients or animals with prion diseases can be amplified and detected through the serial protein misfolding cyclic amplification (sPMCA) or real-time quaking-induced conversion (RT-QuIC) assays. These findings suggest that skin PrP Sc -seeding activity may serve as a biomarker for the diagnosis of prion diseases; however, its utility as a biomarker for prion therapeutics remains largely unknown. Cellulose ethers (CEs, such as TC-5RW), widely used as food and pharmaceutical additives, have recently been shown to prolong the lifespan of prion-infected mice and hamsters. Here we report that in transgenic (Tg) mice expressing hamster cellular prion protein (PrP C ) infected with the 263K prion, the prion-seeding activity becomes undetectable in the skin tissues of TC-5RW-treated Tg mice by both sPMCA and RT-QuIC assays, whereas such prion-seeding activity is readily detectable in the skin of untreated mice. Notably, TC-5RW exhibits an inhibitory effect on the in vitro amplification of PrP Sc in both skin and brain tissues by sPMCA and RT-QuIC. Moreover, we reveal that TC-5RW is able to directly decrease protease-resistant PrP Sc and inhibit the seeding activity of PrP Sc from chronic wasting disease and various human prion diseases. Our results suggest that the level of prion-seeding activity in the skin may serve as a useful biomarker for assessing the therapeutic efficacy of compounds in a clinical trial of prion diseases and that TC-5RW may have the potential for the prevention/treatment of human prion diseases.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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