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

Paper ID Volume ID Publish Year Pages File Format Full-Text
5631 407 2015 12 PDF Available
Title
Transduced PEP-1-PON1 proteins regulate microglial activation and dopaminergic neuronal death in a Parkinson's disease model
Abstract

•PEP-1-PON1 transduces into BV2, SH-SY5Y cells and animal brains.•PEP-1-PON1 protects against LPS exposed BV2 cell death.•PEP-1-PON1 protects against MPP+-induced neurotoxicity in SH-SY5Y cells.•PEP-1-PON1 protects against dopaminergic neuronal cell death in a MPTP-induced PD mice.•PEP-1-PON1 can be a therapeutic agent for inflammation and oxidative stress-related neuronal diseases.

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.

Keywords
Parkinson's disease; PEP-1-PON1; Inflammation; Dopaminergic neuronal death; Oxidative stress; Protein therapy
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Transduced PEP-1-PON1 proteins regulate microglial activation and dopaminergic neuronal death in a Parkinson's disease model
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 64, September 2015, Pages 45–56
Authors
, , , , , , , , , , , , , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us