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: Yeom Pyo Lee, Dae Won Kim, Hye Won Kang, Jae Hyeok Hwang, Hoon Jae Jeong, Eun Jeong Sohn, Mi Jin Kim, Eun Hee Ahn, Min Jea Shin, Duk-Soo Kim, Tae-Cheon Kang, Oh-Shin Kwon, Sung-Woo Cho, Jinseu Park, Won Sik Eum, Soo Young Choi
• Journal: The FEBS journal (FEBS J) Vol. 279 Issue 11 Pg. 1929-42 (Jun 2012) ISSN: 1742-4658 [Electronic] England
• PMID: 22429328 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 The Authors Journal compilation © 2012 FEBS.

Chemical References

• HSP27 Heat-Shock Proteins
• Pep-1 peptide
• Peptides
• Reactive Oxygen Species
• Recombinant Fusion Proteins
• Cysteamine
• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• 1-Methyl-4-phenylpyridinium

Topics

• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (administration & dosage)
• 1-Methyl-4-phenylpyridinium (toxicity)
• Animals
• Cell Death (drug effects)
• Cell Line, Tumor
• Cysteamine (analogs & derivatives, metabolism)
• DNA Fragmentation (drug effects)
• Dopaminergic Neurons (drug effects, metabolism, pathology)
• Escherichia coli
• HSP27 Heat-Shock Proteins (genetics, metabolism)
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Oxidative Stress (drug effects)
• Parkinson Disease, Secondary (chemically induced, drug therapy, metabolism)
• Peptides (genetics, metabolism)
• Reactive Oxygen Species (antagonists & inhibitors)
• Recombinant Fusion Proteins (genetics, metabolism, pharmacology)
• Rotarod Performance Test
• Substantia Nigra (drug effects, metabolism, pathology)