한빛사논문
- 조회859
Yong-Chan Kim#,1,2, Sae-Young Won#,1,2, Byung-Hoon Jeong1,2,*
1Korea Zoonosis Research Institute, Jeonbuk National University, Iksan, Jeonbuk, Republic of Korea.
2Department of Bioactive Material Sciences and Institute for Molecular Biology and Genetics, Jeonbuk National University, Jeonju, Jeonbuk, Republic of Korea.
#Contributed equally.
*Corresponding author.
Abstract
Prion diseases are fatal and incurable neurodegenerative diseases caused by a pathogenic form of prion protein (PrPSc) derived from a cellular form of prion protein (PrPC). Recent studies have reported that aquaporin 4 (AQP4) expression is dramatically upregulated in the brains of individuals with several different prion diseases. Since AQP4 is a key protein of the glymphatic system, which is the perivascular waste clearing system of the brain, and since altered expression of AQP4 has been observed in prion diseases, the glymphatic system may be associated with prion diseases. Thus, investigation of the association between the glymphatic system and prion diseases is important. We identified the expression pattern of glymphatic system-related molecules in prion-infected mice at 7 months post-injection and sporadic Creutzfeldt-Jakob disease (CJD) patients by western blotting and immunohistochemistry (IHC). In addition, we introduced glymphatic system-activated drugs, including dexmedetomidine and clonidine, which are known to increase glymphatic flow and remove brain waste. Then, we evaluated the protective effect of glymphatic system-activated drugs in prion-infected mice by western blotting and survival analysis. We identified altered band patterns of cleaved agrin and upregulation of neurotrypsin expression in prion-infected mice and sporadic CJD patients. We found dramatic clearance of PrPSc and amelioration of astrocytosis in the dexmedetomidine- and clonidine-treated prion-infected mice at 5 months post-injection. In addition, we observed a significantly delayed incubation period in the dexmedetomidine- and clonidine-treated prion-infected mice.
논문정보
- Research article
- 2021년 08월 (BRIC 등록일 2021-08-10)
- 국내 연구진
- 의약학 > 감염의학
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