Restoring cellular copper homeostasis in Alzheimer disease: a novel peptide shuttle is internalized by an ATP-dependent endocytosis pathway involving Rab5- and Rab14-endosomes.

CPPs, or Cell-Penetrating Peptides, offer invaluable utility in disease treatment due to their ability to transport various therapeutic molecules across cellular membranes. Their unique characteristics, such as biocompatibility and low immunogenicity, make them ideal candidates for delivering drugs, genes, or imaging agents directly into cells. This targeted delivery enhances treatment efficacy while minimizing systemic side effects.

Rationally Designed Cu(I) Ligand to Prevent CuAβ-Generated ROS Production in the Alzheimer's Disease Context.

In the context of Alzheimer's disease, copper (Cu) can be loosely bound to the amyloid-β (Aβ) peptide, leading to the formation of CuAβ, which can catalytically generate reactive oxygen species that contribute to oxidative stress. To fight against this phenomenon, the chelation therapy approach has been developed and consists of using a ligand able to remove Cu from Aβ and to redox-silence it, thus stopping the reactive oxygen species (ROS) production. A large number of Cu(II) chelators has been studied, allowing us to define and refine the properties required to design a "good" ligand, but without strong therapeutic outcomes to date.

Redox processes in Cu-binding proteins: the "in-between" states in intrinsically disordered peptides.

We report on a concept that some of us first described a decade ago for pure electron transfer [V. Balland, C. Hureau and J.

Oxidative Damages on the Alzheimer's Related-Aβ Peptide Alters Its Ability to Assemble.

Oxidative stress that can lead to oxidation of the amyloid-β (Aβ) peptide is considered a key feature in Alzheimer's disease (AD), influencing the ability of Aβ to assemble into β-sheet rich fibrils that are commonly found in senile plaques of AD patients. The present study aims at investigating the fallouts of Aβ oxidation on the assembly properties of the Aβ peptide. To accomplish this, we performed kinetics and analysis on an oxidized Aβ (Aβ) peptide, resulting from the attack of reactive oxygen species (ROS) that are formed by the biologically relevant Cu/Aβ/dioxygen/ascorbate system.

Ability of Azathiacyclen Ligands To Stop Cu(Aβ)-Induced Production of Reactive Oxygen Species: [3N1S] Is the Right Donor Set.

Alzheimer's disease (AD) is an incurable neurodegenerative disease that leads to the progressive and irreversible loss of mental functions. The amyloid beta (Aβ) peptide involved in the disease is responsible for the production of damaging reactive oxygen species (ROS) when bound to Cu ions. A therapeutic approach that consists of removing Cu ions from Aβ to alter this deleterious interaction is currently being developed.