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乙醇胺是一种新型抗朊病毒化合物。

Ethanolamine Is a New Anti-Prion Compound.

机构信息

Division of Molecular Neurobiology, The Institute for Enzyme Research (KOSOKEN), Tokushima University, 3-18-15 Kuramoto, Tokushima 770-8503, Japan.

Division of Genome Medicine, Institute of Advanced Medical Sciences, Tokushima University, Tokushima 770-8503, Japan.

出版信息

Int J Mol Sci. 2021 Oct 29;22(21):11742. doi: 10.3390/ijms222111742.

DOI:10.3390/ijms222111742
PMID:34769172
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8584212/
Abstract

Prion diseases are a group of fatal neurodegenerative disorders caused by accumulation of proteinaceous infectious particles, or prions, which mainly consist of the abnormally folded, amyloidogenic prion protein, designated PrP. PrP is produced through conformational conversion of the cellular isoform of prion protein, PrP, in the brain. To date, no effective therapies for prion diseases have been developed. In this study, we incidentally noticed that mouse neuroblastoma N2a cells persistently infected with 22L scrapie prions, termed N2aC24L1-3 cells, reduced PrP levels when cultured in advanced Dulbecco's modified eagle medium (DMEM) but not in classic DMEM. PrP levels remained unchanged in prion-uninfected parent N2aC24 cells cultured in advanced DMEM. These results suggest that advanced DMEM may contain an anti-prion compound(s). We then successfully identified ethanolamine in advanced DMEM has an anti-prion activity. Ethanolamine reduced PrP levels in N2aC24L1-3 cells, but not PrP levels in N2aC24 cells. Also, oral administration of ethanolamine through drinking water delayed prion disease in mice intracerebrally inoculated with RML scrapie prions. These results suggest that ethanolamine could be a new anti-prion compound.

摘要

朊病毒病是一组由蛋白质传染性颗粒（又称朊病毒）积累引起的致命神经退行性疾病，主要由异常折叠的淀粉样朊病毒蛋白组成，称为 PrP。PrP 通过脑内朊病毒蛋白的细胞同工型 PrP 的构象转换产生。迄今为止，尚未开发出针对朊病毒病的有效疗法。在本研究中，我们偶然注意到，持续感染 22L 瘙痒性朊病毒的小鼠神经母细胞瘤 N2a 细胞（称为 N2aC24L1-3 细胞）在高级 Dulbecco 改良 Eagle 培养基（DMEM）中培养时 PrP 水平降低，但在经典 DMEM 中则不会。在高级 DMEM 中培养的未感染朊病毒的亲本 N2aC24 细胞中，PrP 水平保持不变。这些结果表明，高级 DMEM 可能含有抗朊病毒化合物。然后，我们成功地鉴定出高级 DMEM 中的乙醇胺具有抗朊病毒活性。乙醇胺降低了 N2aC24L1-3 细胞中的 PrP 水平，但对 N2aC24 细胞中的 PrP 水平没有影响。此外，通过饮用水口服给予乙醇胺可延迟用 RML 瘙痒性朊病毒颅内接种的小鼠的朊病毒病。这些结果表明，乙醇胺可能是一种新的抗朊病毒化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e3e/8584212/9d24f1804382/ijms-22-11742-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e3e/8584212/a09c50d284d8/ijms-22-11742-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e3e/8584212/64431fb809b6/ijms-22-11742-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e3e/8584212/9d24f1804382/ijms-22-11742-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e3e/8584212/a09c50d284d8/ijms-22-11742-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e3e/8584212/cc76c82711ae/ijms-22-11742-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e3e/8584212/766f7307349b/ijms-22-11742-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e3e/8584212/bfd03e2a0f96/ijms-22-11742-g004.jpg
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