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Le complexe CuII Amyloïde-bêta lié à la Maladie d'Alzheimer :
Etude structurale, thermodynamique et réactivité

Abstract : A peptide called amyloid-beta (Aβ) seems to play a key role in Alzheimer's disease (AD). Aβ is present in healthy humans in a soluble form, but forms aggregates in AD (amyloid plaques). According to the amyloid cascade hypothesis, these aggregates are toxic to neurons and hence lead to their degeneration and the development of AD. The degeneration occurs via the production of reactive oxygen species (ROS). Copper ions play an important role in these processes, because they can bind to Aβ and they are highly accumulated in the plaques. Moreover, copper ions influence the aggregation of amyloid-beta and are supposed to be involved in the ROS production.
Our studies focused on the soluble complex CuII-Aβ. They revealed new insights : (i) Isothermal Titration Calorimetry (ITC) showed two CuII binding sites, with an apparent Kd of 10-7 M and 10-5 M, respectively. (ii) It is know that the three histidine (position 6,13,14) are involved in the complex. EPR showed a 3N/1O environment and 1H-NMR suggests that the Asp in position 1 is involved in the ligation to CuII. So, we propose the carboxylate of the Asp1 as the fourth ligand of copper. (iii) We have shown than CuII-Aβ peptide could generate hydroxyl radicals HO• in the presence of ascorbate. This production has been linked to the redox potentials of complexes. (iv) The influence of copper on the aggregation (kinetic, oligomers formation, type of aggregates) was also studied.
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https://tel.archives-ouvertes.fr/tel-00142748
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Submitted on : Friday, April 20, 2007 - 6:13:53 PM
Last modification on : Friday, March 12, 2021 - 1:32:04 PM
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Luc Guilloreau. Le complexe CuII Amyloïde-bêta lié à la Maladie d'Alzheimer :
Etude structurale, thermodynamique et réactivité. Autre. Université Paul Sabatier - Toulouse III, 2006. Français. ⟨tel-00142748⟩

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