title: PEP-1-heat shock protein 27 protects from neuronal damage in cells and in a Parkinson's disease mouse model.
abstract: Heat shock proteins (HSPs) are a highly conserved family of proteins that are induced in response to various environmental stressors including reactive oxygen species. HSP27 is a chaperone protein with the ability to increase cell survival in response to oxidative stress. Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons. Although the mechanism of PD remains unclear, oxidative stress is known to be important in its pathogenesis. This study investigated the protective effects of PEP-1-HSP27 on neuronal damage induced by 1-methyl-4-phenyl pyridinium (MPP(+) ) in SH-SY5Y cells and in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. PEP-1-HSP27 rapidly entered the cells and protected them against MPP(+) -induced toxicity by inhibiting the reactive oxygen species levels and DNA fragmentation. Furthermore, transduced PEP-1-HSP27 prevented dopaminergic neuronal cell death in the substantia nigra of MPTP-induced PD mouse models. These results demonstrate that PEP-1-HSP27 provides a potential strategy for therapeutic delivery against various diseases and is a potential tool for the treatment of PD.
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon, Korea.
authors.forename: Yeom Pyo
authors.initials: YP
authors.lastname: Lee
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.forename: Hye Won
authors.initials: HW
authors.lastname: Kang
authors.forename: Jae Hyeok
authors.initials: JH
authors.lastname: Hwang
authors.forename: Hoon Jae
authors.initials: HJ
authors.lastname: Jeong
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Sohn
authors.forename: Mi Jin
authors.initials: MJ
authors.lastname: Kim
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Ahn
authors.forename: Min Jea
authors.initials: MJ
authors.lastname: Shin
authors.forename: Duk-Soo
authors.initials: DS
authors.lastname: Kim
authors.forename: Tae-Cheon
authors.initials: TC
authors.lastname: Kang
authors.forename: Oh-Shin
authors.initials: OS
authors.lastname: Kwon
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Cho
authors.forename: Jinseu
authors.initials: J
authors.lastname: Park
authors.forename: Won Sik
authors.initials: WS
authors.lastname: Eum
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage; D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003543:Cysteamine / Q000031:analogs & derivatives* / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004926:Escherichia coli; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D045442:Rotarod Performance Test; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D055551:HSP27 Heat-Shock Proteins; C503924:Pep-1 peptide; D010455:Peptides; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D003543:Cysteamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium