Tyrosol, a simple phenol from EVOO, targets multiple pathogenic mechanisms of neurodegeneration in a C. elegans model of Parkinson's disease

Garcia-Moreno, Jesús Calahorra; Riva, Montserrat Porta de la; Martı́nez-Lara, Esther; Siles, Eva; Cañuelo, Ana

doi:10.1016/j.neurobiolaging.2019.07.003

Cited by 45 publications

(44 citation statements)

References 53 publications

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“…The analysis of dopaminergic neuron degeneration of worms was done by the previous described the fluorescence quantitative method [ 73 ]. After 3 d of treatment at 20 °C, worms were washed three times with M9 buffer and then mounted onto a 2% agar pad on a glass slide, anesthetized with 100 mM sodium azide, before being enclosed with a coverslip.…”

Section: Methodsmentioning

confidence: 99%

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Maackiain Ameliorates 6-Hydroxydopamine and SNCA Pathologies by Modulating the PINK1/Parkin Pathway in Models of Parkinson’s Disease in Caenorhabditis elegans and the SH-SY5Y Cell Line

Tsai

Liu

et al. 2020

IJMS

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The movement disorder Parkinson’s disease (PD) is the second most frequently diagnosed neurodegenerative disease, and is associated with aging, the environment, and genetic factors. The intracellular aggregation of α-synuclein and the loss of dopaminergic neurons in the substantia nigra pars compacta are the pathological hallmark of PD. At present, there is no successful treatment for PD. Maackiain (MK) is a flavonoid extracted from dried roots of Sophora flavescens Aiton. MK has emerged as a novel agent for PD treatment that acts by inhibiting monoamine oxidase B. In this study, we assessed the neuroprotective potential of MK in Caenorhabditis elegans and investigated possible mechanism of this neuroprotection in the human SH-SY5Y cell line. We found that MK significantly reduced dopaminergic neuron damage in 6-hydroxydopamine (6-OHDA)-exposed worms of the BZ555 strain, with corresponding improvements in food-sensing behavior and life-span. In transgenic worms of strain NL5901 treated with 0.25 mM MK, the accumulation of α-synuclein was diminished by 27% (p < 0.01) compared with that in untreated worms. Moreover, in worms and the SH-SY5Y cell line, we confirmed that the mechanism of MK-mediated protection against PD pathology may include blocking apoptosis, enhancing the ubiquitin-proteasome system, and augmenting autophagy by increasing PINK1/parkin expression. The use of small interfering RNA to downregulate parkin expression in vivo and in vitro could reverse the benefits of MK in PD models. MK may have considerable therapeutic applications in PD.

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Section: Methodsmentioning

confidence: 99%

“…Accumulation of α-synuclein protein was measured by using a previously described quantitative fluorescence protocol [ 73 ]. Synchronized NL5901 L3 larvae were cultured on OP50/NGM plates containing 0.04 mg/mL FUDR, with or without the indicated concentrations of MK, for 3 d at 20 °C, and then washed three times with M9 buffer.…”

Section: Methodsmentioning

confidence: 99%

Maackiain Ameliorates 6-Hydroxydopamine and SNCA Pathologies by Modulating the PINK1/Parkin Pathway in Models of Parkinson’s Disease in Caenorhabditis elegans and the SH-SY5Y Cell Line

Tsai

Liu

et al. 2020

IJMS

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“…Antioxidants possess great potential as drugs suitable for the treatment of various diseases related to oxidative stress. In particular, the use of compounds containing phenol structural moiety in the treatment of Alzheimer's disease [32][33][34][35][36], Parkinson´s disease [37][38][39], Huntington´s disease [40,41], and cancer [42][43][44][45] have been extensively studied in the last two years. Their structural diversity provides many possibilities for the design and synthesis of new, highly effective agents.…”

Section: Introductionmentioning

confidence: 99%

Antioxidative Activity of 1,3,5-Triazine Analogues Incorporating Aminobenzene Sulfonamide, Aminoalcohol/Phenol, Piperazine, Chalcone, or Stilbene Motifs

et al. 2020

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A series of 1,3,5-triazine analogues, incorporating aminobenzene sulfonamide, aminoalcohol/phenol, piperazine, chalcone, or stilbene structural motifs, were evaluated as potential antioxidants. The compounds were prepared by using step-by-step nucleophilic substitution of chlorine atoms in starting 2,4,6-trichloro-1,3,5-triazine. Reactions were catalyzed by Cu(I)-supported on a weakly acidic resin. The radical scavenging activity was determined in terms of %inhibition activity and EC50, using the ABTS method. Trolox and ascorbic acid (ASA) were used as standards. In the lowest concentration 1 × 10−4 M, the %inhibition activity values at 0 min were comparable with both standards at least for 10 compounds. After 60 min, compounds 5, 6, 13, and 25 showed nearly twice %inhibition (73.44–87.09%) in comparison with the standards (Trolox = 41.49%; ASA = 31.07%). Values of EC50 at 60 min (17.16–27.78 μM) were 5 times lower for compounds 5, 6, 13, and 25 than EC50 of both standards (trolox = 178.33 μM; ASA = 147.47 μM). Values of EC50 correlated with %inhibition activity. Based on these results, the presented 1,3,5-triazine analogues have a high potential in the treatment of illnesses caused or related to oxidative stress.

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“…Finally, tyrosol, a simple phenol present in Extra Virgin Olive Oil, was also shown to be effective by reducing α-syn inclusions in a C. elegans model of PD. Moreover, in this in vivo model, Tyrosol had a protective effect on dopaminergic neurons, reduced ROS level and promoted the expression of specific chaperones and antioxidant enzymes [382].…”

Section: Polyphenolsmentioning

confidence: 69%

Targeting α-Synuclein for PD Therapeutics: A Pursuit on All Fronts

et al. 2020

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Parkinson’s Disease (PD) is characterized both by the loss of dopaminergic neurons in the substantia nigra and the presence of cytoplasmic inclusions called Lewy Bodies. These Lewy Bodies contain the aggregated α-synuclein (α-syn) protein, which has been shown to be able to propagate from cell to cell and throughout different regions in the brain. Due to its central role in the pathology and the lack of a curative treatment for PD, an increasing number of studies have aimed at targeting this protein for therapeutics. Here, we reviewed and discussed the many different approaches that have been studied to inhibit α-syn accumulation via direct and indirect targeting. These analyses have led to the generation of multiple clinical trials that are either completed or currently active. These clinical trials and the current preclinical studies must still face obstacles ahead, but give hope of finding a therapy for PD with time.

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Tyrosol, a simple phenol from EVOO, targets multiple pathogenic mechanisms of neurodegeneration in a C. elegans model of Parkinson's disease

Cited by 45 publications

References 53 publications

Maackiain Ameliorates 6-Hydroxydopamine and SNCA Pathologies by Modulating the PINK1/Parkin Pathway in Models of Parkinson’s Disease in Caenorhabditis elegans and the SH-SY5Y Cell Line

Maackiain Ameliorates 6-Hydroxydopamine and SNCA Pathologies by Modulating the PINK1/Parkin Pathway in Models of Parkinson’s Disease in Caenorhabditis elegans and the SH-SY5Y Cell Line

Antioxidative Activity of 1,3,5-Triazine Analogues Incorporating Aminobenzene Sulfonamide, Aminoalcohol/Phenol, Piperazine, Chalcone, or Stilbene Motifs

Targeting α-Synuclein for PD Therapeutics: A Pursuit on All Fronts

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