title: PEP-1-PEA-15 protects against toxin-induced neuronal damage in a mouse model of Parkinson's disease.
abstract: BACKGROUND
  PEA-15 is abundantly expressed in both neurons and astrocytes throughout the brain. It is a multifunctional protein with the ability to increase cell survival via anti-apoptotic and anti-proliferative properties. However, the function of PEA-15 in neuronal diseases such as Parkinson's disease (PD) remains unclear. In this study, we investigated the protective effects of PEA-15 on neuronal damage induced by MPP(+) in neuroblastoma SH-SY5Y and BV2 microglia cells and in a MPTP-induced PD mouse model using cell-permeable PEP-1-PEA-15.
  
  
  METHODS
  PEP-1-PEA-15 was purified using affinity chromatography. Cell viability and DNA fragmentation were examined by MTT assay and TUNEL staining. Dopaminergic neuronal cell death in the animal model was examined by immunohistochemistry.
  
  
  RESULTS
  PEP-1-PEA-15 transduced into the SH-SY5Y and BV2 cells in a time- and dose-dependent manner. Transduced PEP-1-PEA-15 protected against MPP(+)-induced toxicity by inhibiting intracellular ROS levels and DNA fragmentation. Further, it enhanced the expression levels of Bcl-2 and caspase-3 while reducing the expression levels of Bax and cleaved caspase-3. We found that PEP-1-PEA-15 transduced into the substantia nigra and prevented dopaminergic neuronal cell death in a MPTP-induced PD mouse. Also, we showed the neuroprotective effects in the model by demonstrating that treatment with PEP-1-PEA-15 ameliorated MPTP-induced behavioral dysfunctions and increased dopamine levels in the striatum.
  
  
  CONCLUSIONS
  PEP-1-PEA-15 can efficiently transduce into cells and protects against neurotoxin-induced neuronal cell death in vitro and in vivo.
  
  
  CONCLUSIONS
  These results demonstrate the potential for PEP-1-PEA-15 to provide a new strategy for protein therapy treatment of a variety of neurodegenerative diseases including PD.
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Ahn
authors.affiliation: Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Kangnung-Wonju National University, Gangneung 210-702, Republic of Korea.
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Min Jea
authors.initials: MJ
authors.lastname: Shin
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Hye Ri
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: So Mi
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Su Jung
authors.initials: SJ
authors.lastname: Woo
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Seon Ae
authors.initials: SA
authors.lastname: Eom
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Hyo Sang
authors.initials: HS
authors.lastname: Jo
authors.affiliation: Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si 330-090, Republic of Korea.
authors.forename: Duk-Soo
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea.
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Cho
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Jinseu
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea. Electronic address: wseum@hallym.ac.kr.
authors.forename: Won Sik
authors.initials: WS
authors.lastname: Eum
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea. Electronic address: sychoi@hallym.ac.kr.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D003543:Cysteamine / Q000031:analogs & derivatives*; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010300:Parkinson Disease / Q000628:therapy*; D010455:Peptides / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D014161:Transduction, Genetic
chemical_list: D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; C092039:PEA15 protein, human; C503924:Pep-1 peptide; D010455:Peptides; D010750:Phosphoproteins; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D003543:Cysteamine; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Neurotoxin; Oxidative stress; PEP-1-Phosphoprotein enriched in astrocytes 15; Parkinson's disease; Protein therapy