Neuroprotective Effect of a DJ-1 Based Peptide in a Toxin Induced Mouse Model of Multiple System Atrophy

PLoS One. 2016 Feb 22;11(2):e0148170. doi: 10.1371/journal.pone.0148170. eCollection 2016.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Male
  • Mice
  • Microtubule-Associated Proteins / chemistry*
  • Multiple System Atrophy / chemically induced
  • Multiple System Atrophy / drug therapy*
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / therapeutic use*
  • Nitro Compounds / pharmacology
  • PC12 Cells
  • Peptides / chemistry*
  • Peptides / therapeutic use*
  • Propionates / pharmacology
  • Rats

Substances

  • Microtubule-Associated Proteins
  • Neuroprotective Agents
  • Nitro Compounds
  • Peptides
  • Propionates
  • 3-nitropropionic acid

Grant support

UGH Pharma, Inc. supplied the peptide (ND-13) used in the studies. This study also received funds as a scholarship from Mr. Martin Davis, a private donor. Other than the peptide (ND-13) which was supplied by UGH Pharma, Inc., and these scholarship funds, the authors received no specific funding for this work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.