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Transduced PEP-1-PON1 proteins regulate microglial activation and dopaminergic neuronal death in a Parkinson's disease model

Authors
Kim, Mi JinPark, MeeyoungKim, Dae WonShin, Min JeaSon, OraJo, Hyo SangYeo, Hyeon JiCho, Su BinPark, Jung HwanLee, Chi HemKim, Duk-SooKwon, Oh-ShinKim, JoonHan, Kyu HyungPark, JinseuEum, Won SikChoi, Soo Young
Issue Date
9월-2015
Publisher
ELSEVIER SCI LTD
Keywords
Parkinson' s disease; PEP-1-PON1; Inflammation; Dopaminergic neuronal death; Oxidative stress; Protein therapy
Citation
BIOMATERIALS, v.64, pp.45 - 56
Indexed
SCIE
SCOPUS
Journal Title
BIOMATERIALS
Volume
64
Start Page
45
End Page
56
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/92665
DOI
10.1016/j.biomaterials.2015.06.015
ISSN
0142-9612
Abstract
Parkinson's disease (PD) is an oxidative stress-mediated neurodegenerative disorder caused by selective dopaminergic neuronal death in the midbrain substantia nigra. Paraoxonase 1 (PON1) is a potent inhibitor of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) against oxidation by destroying biologically active phospholipids with potential protective effects against oxidative stress-induced inflammatory disorders. In a previous study, we constructed protein transduction domain (PTD) fusion PEP-1-PON1 protein to transduce PON1 into cells and tissue. In this study, we examined the role of transduced PEP-1-PON1 protein in repressing oxidative stress-mediated inflammatory response in microglial BV2 cells after exposure to lipopolysaccharide (LPS). Moreover, we identified the functions of transduced PEP-1-PON1 proteins which include, mitigating mitochondrial damage, decreasing reactive oxidative species (ROS) production, matrix metalloproteinase-9 (MMP-9) expression and protecting against 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity in SH-SY5Y cells. Furthermore, transduced PEP-1-PON1 protein reduced MMP-9 expression and protected against dopaminergic neuronal cell death in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice model. Taken together, these results suggest a promising therapeutic application of PEP-1-PON1 proteins against PD and other inflammation and oxidative stress-related neuronal diseases. (C) 2015 Elsevier Ltd. All rights reserved.
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