title: Neuroprotective Effect of a DJ-1 Based Peptide in a Toxin Induced Mouse Model of Multiple System Atrophy.
abstract: Multiple System Atrophy (MSA) is a sporadic neurodegenerative disorder characterized by parkinsonism, cerebellar ataxia and dysautonomia, in various combinations. In MSA with parkinsonism (MSA-P), the degeneration is mainly restricted to the substantia nigra pars compacta and putamen. Studies have identified alterations in DJ-1 (PARK7), a key component of the anti-oxidative stress response, in Parkinson's disease (PD) and MSA patients. Previously we have shown that a short DJ-1-based peptide named ND-13, protected cultured cells against neurotoxic insults and improved behavioral outcome in animal models of Parkinson's disease (PD). In this study, we used the 3-Nitropropionic acid (3-NP)-induced mouse model of MSA and treated the animals with ND-13 in order to evaluate its therapeutic effects. Our results show that ND-13 protects cultured cells against oxidative stress generated by the mitochondrial inhibitor, 3-NP. Moreover, we show that ND-13 attenuates nigrostriatal degeneration and improves performance in motor-related behavioral tasks in 3-NP-treated mice. Our findings suggest a rationale for using ND-13 as a promising therapeutic approach for treatment of MSA.
authors.affiliation: Sagol School of Neuroscience, Tel-Aviv University, Tel Aviv, Israel.
authors.forename: Micaela Johanna
authors.initials: MJ
authors.lastname: Glat
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: Yael
authors.initials: Y
authors.lastname: Barhum
authors.affiliation: Sagol School of Neuroscience, Tel-Aviv University, Tel Aviv, Israel.|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; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000737:chemistry*; D019578:Multiple System Atrophy / Q000139:chemically induced / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000627:therapeutic use*; D009574:Nitro Compounds / Q000494:pharmacology; D016716:PC12 Cells; D010455:Peptides / Q000737:chemistry* / Q000627:therapeutic use*; D011422:Propionates / Q000494:pharmacology; D051381:Rats
chemical_list: D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; D009574:Nitro Compounds; D010455:Peptides; D011422:Propionates; C015392:3-nitropropionic acid