구.농수식품
- 조회444
Yong‑Chan Kim1,2, Junbeom Lee3, Dae‑Weon Lee3,4,* and Byung‑Hoon Jeong1,2,*
1Korea Zoonosis Research Institute, Jeonbuk National University, Iksan, Jeonbuk 54531, Republic of Korea. 2Department of Bioactive Material Sciences and Institute for Molecular Biology and Genetics, Jeonbuk National University, Jeonju, Jeonbuk 54896, Republic of Korea. 3Metabolomics Research Center for Functional Materials, Kyungsung University, Busan 48434, Republic of Korea. 4Department of Bio‑Safety, Kyungsung University, Busan 48434, Republic of Korea.
*Correspondence to Dae-Weon Lee or Byung-Hoon Jeong.
Abstract
Prion diseases are transmissible spongiform encephalopathies induced by the abnormally-folded prion protein (PrPSc), which is derived from the normal prion protein (PrPC). Previous studies have reported that lipid rafts play a pivotal role in the conversion of PrPC into PrPSc, 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 PrPSc 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.
논문정보
- Research article
- 2021년 07월 (BRIC 등록일 2021-09-14)
- 국내 연구진
- 의약학 > 감염의학
- 구・농수식품
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