The aging of the Western Society is leading to the increase in the prevalence of neurodegenerative disorders (where neural cells suffer functional or sensory loss). Apart from several other environmental or genetic factors, oxidative stress lead to free radical attack on neural cells and contributes significantly to increase neurodegeneration. Therefore, the relationship between the anti-oxidant capacity of natural compounds and their activity towards these disorders became a case of study, namely, in their capacity to inhibit protein aggregation [1].

Machado-Joseph disease (MJD) is a genetic-based neurodegenerative disorder characterized by progressive impairment in movement, including difficulty in motor coordination and balance (ataxia). In MJD the aggregation of the disease-specific protein ataxin-3 (ATXN3) puts protein aggregation (and protein homeostasis) at the centre of the stage in what their pathogenesis is concerned [2].

Initial experiments using C. elegans modelof mutant ataxin-3(genetically modified to present MJD characteristic features, e.g. movement impairment and ataxin-3 aggregates in the neurons) revealed that animals incubated with cork water extract (CWE), at a concentration of 500μg/mL, lead to a reduction of the locomotion deficit and a partial inhibition of ataxin-3 aggregation. However, it was difficult to associate this activity with a specific compound. Herein we used preparative HPLC to obtain a series of simpler fractions and isolated compounds (9 in total) and to test them in the same animal model. We found that the compound vescalagin purified from CWE (one of the pHPLC fractions) present a significantly higher capacity to inhibit the MJD pathogenesis in the same C. elegans model at much lower concentrations than the original CWE extract (i.e. 22μg/mL). Our results clearly indicate that vescalagin obtained from CWE is one of the responsibles for the activity of CWE reducing the movement impairment of the C. elegans nematodes (genetically modified to present MJD features).

REFERENCES

1.         Butterfield, D.A. and J. Kanski, Brain protein oxidation in age-related neurodegenerative disorders that are associated with aggregated proteins. Mechanisms of Ageing and Development, 2001. 122(9): p. 945-962.

2.         Lee, H.C. and Y.H. Wei, Mitochondria and aging. Adv Exp Med Biol, 2012. 942: p. 311-27.