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Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease
Published on: January 7, 2014
Bioactivated Glucoraphanin Exerts a Potential Protective Effect in an In Vitro Model of Parkinson's Disease: A
Agnese Gugliandolo1, Claudia Muscarà1, Alessia Floramo1
1IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy.
Abstract:
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by both motor and non-motor symptoms. Oxidative stress is involved in disease pathogenesis, with the consequent damage to DNA. Nowadays, phytocompounds attract much interest for their capacity to modulate some of the pathogenic mechanisms of PD. Glucosinolates (GLs) and their derivatives, isothiocyanate (ITC), obtained by GLs hydrolysis by myrosinase (MYR), showed neuroprotective properties. In this study, we evaluated the protective effects of pre- and post-treatment with the GL glucoraphanin (GRA) bioactivated with MYR in an in vitro model of PD, namely differentiated SH-SY5Y cells treated with the toxin MPP+. With this aim, we performed transcriptomic analysis using next-generation sequencing (NGS). We observed that GRA + MYR pre-treatment modulated Biological Process (BP) of Gene Ontology (GO) and Reactome pathways associated with oxidative stress response and DNA repair mechanisms. In the post-treatment group, BP and pathways associated with DNA processes were also overrepresented in association with those correlated to oxidative stress. Indeed, some differentially expressed genes associated with oxidative stress response were upregulated, such as SOD1, whose protein levels also increased. The results of this exploratory study suggested that GRA + MYR may induce protective effects and, in particular, pre-treatment may modulate genes involved in DNA repair, while the post-treatment may exert a protective action against oxidative stress.
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