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PLoS One. 2015 May 29;10(5):e0127549. doi: 10.1371/journal.pone.0127549. eCollection 2015.

A DJ-1 Based Peptide Attenuates Dopaminergic Degeneration in Mice Models of Parkinson's Disease via Enhancing Nrf2.

Author information

1
Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Petach Tikva, Israel; Department of Neurology, Rabin Medical Center, Beilinson Campus, Petach Tikva, Israel.
2
Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Petach Tikva, Israel.
3
Division of Medicinal Chemistry, Department of Chemistry, Faculty of Exact Sciences, Bar-Ilan University, Ramat-Gan, Israel.

Abstract

Drugs currently used for treating Parkinson's disease patients provide symptomatic relief without altering the neurodegenerative process. Our aim was to examine the possibility of using DJ-1 (PARK7), as a novel therapeutic target for Parkinson's disease. We designed a short peptide, named ND-13. This peptide consists of a 13 amino acids segment of the DJ-1-protein attached to 7 amino acids derived from TAT, a cell penetrating protein. We examined the effects of ND-13 using in vitro and in vivo experimental models of Parkinson's disease. We demonstrated that ND-13 protects cultured cells against oxidative and neurotoxic insults, reduced reactive oxygen species accumulation, activated the protective erythroid-2 related factor 2 system and increased cell survival. ND-13 robustly attenuated dopaminergic system dysfunction and in improved the behavioral outcome in the 6-hydroxydopamine mouse model of Parkinson's disease, both in wild type and in DJ-1 knockout mice. Moreover, ND-13 restored dopamine content in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model. These findings validate DJ-1 as a promising therapeutic target in Parkinson's disease and identify a novel peptide with clinical potential, which may be significant for a broader range of neurological diseases, possibly with an important impact for the neurosciences.

PMID:
26024237
PMCID:
PMC4449207
DOI:
10.1371/journal.pone.0127549
[Indexed for MEDLINE]
Free PMC Article

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