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Parkinson’s disease (PD) is a common neurodegenerative disorder involving α-synuclein (α-syn) aggregation, oxidative stress, dysregulation of redox metal homeostasis, and neurotoxicity. The present study aims to investigate for the first time the effect of tyrosol (TYR), a simple phenol present in extra-virgin olive oil (EVOO), on α-syn aggregation in a Caenorhabditis elegans model of PD and evaluate its potential to prevent toxicity, neurodegeneration, and oxidative stress.

Methods

For the paralysis assay in liquid culture, the C. elegans strains N2 and NL5901 were used. The strain NL5901 overexpresses α-syn:YFP within worm body wall muscle cells and also exhibits age dependent mobility defects associated with α-syn:YFP aggregation. For this test, synchronized populations of worms were obtained using hypochlorite extraction. Worms were grown on solid media up to day 1 of adulthood. FUDR 0.12mM was added when worms reached the L4 stage. At adult day 1, N2 or NL5901 worms per well were transferred to S-medium with OP50 (OD = 0.5) in a flat bottom 96-well plate at 20ºC. TYR 1 mM was added and locomotion under control and treatment conditions was assessed for 90 minutes after 3, 7, 9, and 11 days using WMicrotracker.  A total of 180 worms were used per experimental condition.

Results

As shown in Fig.3, NL5901 strain exhibits a premature and progressive decline in body movement compared with the wild-type strain N2 (Fig.3A). This decline becomes more evident by adult day 7 in both, control, and TYR treated NL5901 nematodes. However, by adult day 9,1mM TYR treated nematodes exhibited a significantly faster body movement as compared with untreated controls (nº of activity counts per 30 minutes: control 7.7±1.81 vs. TYR 1mM 20.9±5.62; t-test *p=0.0364) (Fig.3B). By adult day 11, both groups showed a similar level of body movements, close to 100% paralysis.

Neurotherapeutics . 2019 Oct;16(4):1149-1166. doi: 10.1007/s13311-019-00765-w.

Bose P, Tremblay E, Maois C, Narasimhan V, Armstrong GAB, Liao M, Parker JA, Robitaille R, Wen XY, Barden C, Drapeau P.