Thèses

Jeudi 5 Décembre 2024 à 10h00.

Development

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Directeur de thèse / thesis Director :
François Lux,
Laurent David

Membres du jury / jury members :
Stéphane Roux,
Catherine Faure,
Anayancy Osorio-Madrazo,
Thomas Trimaille,
Alexandra Montembault,
Olivier Tillement

Résumé / Abstract :
Metal homeostasis plays a crucial role in maintaining human health. Current research on neurodegenerative diseases suggests that metal dyshomeostasis actively contributes to the pathogenesis and progression of conditions such as Parkinson's and Alzheimer's diseases. Excess free metals in the brain can have deleterious effects on the body, including oxidative damage through the production of hydroxyl radicals, inflammation, and disruption of biological processes due to altered protein and enzyme conformations.
Systemic metal dyshomeostasis has traditionally been treated with chelation therapy. However, this approach presents several challenges for treating brain metal dyshomeostasis, such as the need for high chelator doses, which can lead to adverse effects, and the non-localized nature of chelation.
Many neurodegenerative diseases currently lack effective cures, and available treatments primarily focus on symptom management. Therefore, the aim of this thesis is to develop a chelating material capable of providing localized and specific metal extraction in particular for iron.
To achieve this goal, multiple chelating polymers were synthesized by functionalization with chelating groups. These polymers were then used to develop various chelating materials, which were thoroughly characterized to assess their mechanical properties and chelating efficacy. Finally, in-vivo applications of these materials were evaluated to explore their potential as novel treatments for localized metal extraction in neurodegenerative diseases.

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