Hydroxytyrosol and Dopamine Metabolites: Anti-aggregative Effect and Neuroprotective Activity Against α-synuclein-induced Toxicity
|Author/s||Gallardo Fernández, Marta
Hornedo Ortega, Ruth
Cerezo López, Ana Belén
Troncoso González, Ana María
García Parrilla, María del Carmen
|Department||Universidad de Sevilla. Departamento de Nutrición y Bromatología, Toxicología y Medicina Legal|
|Abstract||The abnormal aggregation of the α-synuclein (αsyn) protein is involved in the formation of Lewy bodies in the brain of patients suffering from Parkinson disease (PD). Hydroxytyrosol (HT), a polyphenolic compound present ...
The abnormal aggregation of the α-synuclein (αsyn) protein is involved in the formation of Lewy bodies in the brain of patients suffering from Parkinson disease (PD). Hydroxytyrosol (HT), a polyphenolic compound present in olives, olive oil, and wine, has been shown to inhibit aggregation and destabilise the αsyn aggregates, preventing neuronal cell death. However, very limited data have been published on the study of its metabolites. Therefore, this study investigated the capacity of the metabolites 3,4-dihydroxyphenylacetaldehyde (DOPAL), 4-hydroxy-3-methoxyphenylethanol (MOPET), and 3-methoxy-4-hydroxyphenylacetaldehyde (MOPAL) to prevent the aggregation and toxic effects of αsyn fibrils. In vitro techniques, such as Thioflavin T (ThT), Transmission Electronic Microscopy (TEM), electrophoresis, thiazolyl blue tetrazolium bromide (MTT), and Real-Time PCR (RT-PCR) were used. Our results show that among these three metabolites, DOPAL exerts the greatest effect, preventing aggregation and αsyn-induced neurotoxicity. In fact, DOPAL has the ability to completely inhibit αsyn fibril formation at low doses. Moreover, this metabolite has a potent destabilising effect on the αsyn fibrils. Concerning neuroprotection, DOPAL can counteract the toxicity induced by αsyn. The vitagene expression results show a possible relationship between the neuroprotection mechanism exhibited by DOPAL and the modulation of SIRT-2 and Hsp70.
|Funding agencies||Ministerio de Ciencia, Innovación y Universidades (MICINN). España
Ministerio de Ciencia e Innovación (MICIN). España
|Citation||Gallardo Fernández, M., Hornedo Ortega, R., Cerezo López, A.B., Troncoso González, A.M. y García Parrilla, M.d.C. (2023). Hydroxytyrosol and Dopamine Metabolites: Anti-aggregative Effect and Neuroprotective Activity Against α-synuclein-induced Toxicity. Food and Chemical Toxicology, 171, 113542. https://doi.org/10.1016/j.fct.2022.113542.|