大规模脂质组学分析鉴定出朊病毒病的新型潜在生物标志物，并突出了脂筏相关途径。
Large-scale lipidomic profiling identifies novel potential biomarkers for prion diseases and highlights lipid raft-related pathways.
机构信息
Korea Zoonosis Research Institute, Jeonbuk National University, Iksan, Jeonbuk, 54531, Republic of Korea.
Department of Bioactive Material Sciences and Institute for Molecular Biology and Genetics, Jeonbuk National University, Jeonju, Jeonbuk, 54896, Republic of Korea.
出版信息
Vet Res. 2021 Jul 21;52(1):105. doi: 10.1186/s13567-021-00975-1.
Prion diseases are transmissible spongiform encephalopathies induced by the abnormally-folded prion protein (PrP), which is derived from the normal prion protein (PrP). Previous studies have reported that lipid rafts play a pivotal role in the conversion of PrP into PrP, and several therapeutic strategies targeting lipids have led to prolonged survival times in prion diseases. In addition, phosphatidylethanolamine, a glycerophospholipid member, accelerated prion disease progression. Although several studies have shown that prion diseases are significantly associated with lipids, lipidomic analyses of prion diseases have not been reported thus far. We intraperitoneally injected phosphate-buffered saline (PBS) or ME7 mouse prions into mice and sacrificed them at different time points (3 and 7 months) post-injection. To detect PrP in the mouse brain, we carried out western blotting analysis of the left hemisphere of the brain. To identify potential novel lipid biomarkers, we performed lipid extraction on the right hemisphere of the brain and liquid chromatography mass spectrometry (LC/MS) to analyze the lipidomic profiling between non-infected mice and prion-infected mice. Finally, we analyzed the altered lipid-related pathways by a lipid pathway enrichment analysis (LIPEA). We identified a total of 43 and 75 novel potential biomarkers at 3 and 7 months in prion-infected mice compared to non-infected mice, respectively. Among these novel potential biomarkers, approximately 75% of total lipids are glycerophospholipids. In addition, altered lipids between the non-infected and prion-infected mice were related to sphingolipid, glycerophospholipid and glycosylphosphatidylinositol (GPI)-anchor-related pathways. In the present study, we found novel potential biomarkers and therapeutic targets of prion disease. To the best of our knowledge, this study reports the first large-scale lipidomic profiling in prion diseases.
朊病毒病是由异常折叠的朊病毒蛋白（PrP）引起的传染性海绵状脑病，该蛋白源自正常的朊病毒蛋白（PrP）。先前的研究表明，脂筏在 PrP 转化为 PrP 过程中发挥关键作用，并且几种针对脂质的治疗策略导致朊病毒病的存活时间延长。此外，作为甘油磷脂成员的磷脂酰乙醇胺加速了朊病毒病的进展。尽管有几项研究表明朊病毒病与脂质密切相关，但迄今为止尚未报道关于朊病毒病的脂质组学分析。我们将磷酸盐缓冲盐水（PBS）或 ME7 小鼠朊病毒通过腹腔注射到小鼠体内，并在注射后不同时间点（3 个月和 7 个月）处死它们。为了检测小鼠脑中的 PrP，我们对左半脑进行了 Western blot 分析。为了鉴定潜在的新型脂质生物标志物，我们对右半脑进行了脂质提取，并通过液相色谱质谱（LC/MS）分析了非感染小鼠和朊病毒感染小鼠之间的脂质组学图谱。最后，我们通过脂质途径富集分析（LIPEA）分析了改变的脂质相关途径。与非感染小鼠相比，在感染朊病毒的小鼠中，我们在 3 个月和 7 个月时分别鉴定出了 43 种和 75 种新型潜在生物标志物。在这些新型潜在生物标志物中，大约 75％的总脂质是甘油磷脂。此外，非感染和朊病毒感染小鼠之间的改变脂质与鞘脂、甘油磷脂和糖基磷脂酰肌醇（GPI）锚定相关途径有关。在本研究中，我们发现了朊病毒病的新型潜在生物标志物和治疗靶标。据我们所知，这项研究报告了朊病毒病中首次进行的大规模脂质组学分析。
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