title: A DJ-1 Based Peptide Attenuates Dopaminergic Degeneration in Mice Models of Parkinson's Disease via Enhancing Nrf2.
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.
authors.affiliation: 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.
authors.forename: Nirit
authors.initials: N
authors.lastname: Lev
authors.affiliation: Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Petach Tikva, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Barhum
authors.affiliation: Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Petach Tikva, Israel.
authors.forename: Tali
authors.initials: T
authors.lastname: Ben-Zur
authors.affiliation: Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Petach Tikva, Israel.
authors.forename: Israel
authors.initials: I
authors.lastname: Aharony
authors.affiliation: Division of Medicinal Chemistry, Department of Chemistry, Faculty of Exact Sciences, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Lena
authors.initials: L
authors.lastname: Trifonov
authors.affiliation: Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Petach Tikva, Israel.
authors.forename: Noa
authors.initials: N
authors.lastname: Regev
authors.affiliation: 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.
authors.forename: Eldad
authors.initials: E
authors.lastname: Melamed
authors.affiliation: Division of Medicinal Chemistry, Department of Chemistry, Faculty of Exact Sciences, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Arie
authors.initials: A
authors.lastname: Gruzman
authors.affiliation: Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Petach Tikva, Israel.
authors.forename: Daniel
authors.initials: D
authors.lastname: Offen
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D020267:MPTP Poisoning / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells; D010455:Peptides / Q000494:pharmacology*; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D000071617:Protein Deglycase DJ-1; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D015513:Oncogene Proteins; D010455:Peptides; D017382:Reactive Oxygen Species; D054464:Peroxiredoxins; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1; D004298:Dopamine