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Article Dans Une Revue International Journal of Molecular Sciences Année : 2024

The 75–99 C-Terminal Peptide of URG7 Protein Promotes α-Synuclein Disaggregation

Résumé

Up Regulation Gene seven (URG7) is the pseudogene 2 of the transporter ABCC6. The translated URG7 protein is localized with its single transmembrane α-helix in the endoplasmic reticulum (ER) membrane, orienting the N- and C-terminal regions in the lumen and cytoplasm, respectively, and it plays a crucial role in the folding of ER proteins. Previously, the C-terminal region of URG7 (PU, residues 75–99) has been shown to modify the aggregation state of α-synuclein in the lysate of HepG2 cells. PU analogs were synthesized, and their anti-aggregation potential was tested in vitro on α-synuclein obtained using recombinant DNA technology. Circular dichroism (CD), differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy, and microscopic techniques were used to assess the sample’s behavior. The results show that the peptides studied by themselves are prone to clathrate-like structure formation of variable stability. Aggregation of α-synuclein is accompanied by desolvation of its peptide chain and an increase in intermolecular β-sheets. The PU analogs all interact with α-synuclein aggregates and those possessing the most stable clathrate-like structures have the highest disaggregating effect. These findings suggest that the C-terminal region of URG7 may have a role in interacting and modulating α-synuclein structures and could be used to generate interesting therapeutic candidates as disaggregators of α-synuclein.
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hal-04401942 , version 1 (18-01-2024)

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Jany Dandurand, Magnus Monné, Valérie Samouillan, Martina Rosa, Alessandro Laurita, et al.. The 75–99 C-Terminal Peptide of URG7 Protein Promotes α-Synuclein Disaggregation. International Journal of Molecular Sciences, 2024, 25 (2), pp.1135. ⟨10.3390/ijms25021135⟩. ⟨hal-04401942⟩
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