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.
Highlights
Multiple System Atrophy (MSA) is a sporadic neurodegenerative disease affecting 4–5 people per 100,000 individuals
The present study describes the effect of treatment with a short DJ1-based peptide, ND-13, on a toxin-induced mouse model of MSA, which mimics the pattern of cell loss, observed in MSA patients
We demonstrate that ND-13 protects cells and rescues mitochondrial function from the toxic effect of 3-Nitropropionic acid (3-NP)
Summary
Multiple System Atrophy (MSA) is a sporadic neurodegenerative disease affecting 4–5 people per 100,000 individuals. The disease is most often diagnosed after the age of 60, with a mean survival of 6–9 years after the diagnosis [1], [2]. MSA is classified as two subtypes: MSA with Parkinsonism (MSA-P), and MSA with cerebellar ataxia (MSA-C). In MSA-C the cerebellum is the main locus of neurodegeneration, and the principal symptom is poor coordination [3]. These two MSA subtypes share the same autonomic dysfunctions that correlate with neurodegeneration in the autonomic brain stem centers, intermediolateral cell columns, and Onuf’s nucleus in the spinal cord [4], [5]
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