|Doctorant :||Lucia Emanueli SCHIMITH|
|Directeur de thèse :||APPEL HORT Mariana (FURG, Brésil)|
|co-directeur de thèse :||Corinne ANDRE-MIRAL , Maître de conférences Université|
|Financement :||FURG (Brésil)|
Parkinson’s disease (PD) is a progressive disease and the second most common neurodegenerative disorder. Pathologically, PD is characterized by the loss of dopaminergic neurons of the substantia nigra and α-synuclein aggregation which lead to motor and cognitive dysfunction. Is believed that other pathways may also be involved such as oxidative stress and neuroinflammation and can also affect other neuronal connections. Currently, there are no therapeutic alternatives able to cure PD. Pharmacological therapy options are focused on symptoms relief and management. Therefore, exploring molecules that can act in the prevention or treatment of PD is necessary. Resveratrol has attracted attention for its anti-inflammatory and antioxidant activities, but its therapeutic effectiveness is limited due its low solubility in aqueous system and low bioavailability. Molecule glycosylation via synthetic induction of structural optimization reactions using enzymes appears as an alternative, guaranteeing specify and regioselectivity.
First, we aim to synthesize and controlled functionalize the resveratrol molecule through enzymatic pathways. This part of the work will be done in US2B, Nantes Université, France. The implementation of such a process will increase the solubility and bioavailability of these functionalized compounds, being able to potentiate their biological responses, allowing specific therapeutic applications. We also purpose to predict the pharmacokinetic parameters of resveratrol and its glycosylated forms, as well as its molecular interactions with PD targets using in silico approaches. Furthermore, we will evaluate the toxicity and effects of resveratrol glycosylation in a zebrafish (Danio rerio) in vivo experimental model of PD at the Universidade Federal do Rio Grande, Brazil.
Dans: Results in Chemistry, p. 100956, 2023.
Dans: Phytotherapy Research, vol. 36, no. 7, p. 2852–2877, 2022.
Dans: Neurotoxicity Research, p. 1–27, 2022.
Dans: Frontiers in Aging Neuroscience, vol. 12, p. 103, 2020, ISSN: 1663-4365.