Novel Aβ/Prion chimera peptides: studies on the inhibition of the Aβ fibrillogenesis and the role of transition metal ions.

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder leading to memory loss and progressive decline in cognitive ability. The main component of these plaques is the 40–42-amino acid residue amyloid-β (Aβ) peptide. A number of studies indicate that peptides fragments corresponding to amino acid sequences from the N-terminal domain of the human prion protein (hPrP), are able to interact with Aβ by recognition motifs and/or the formation of ternary prion peptides/Cu(II)/Aβ complexes. Identification of peptide fragments of hPrP that retain the ability to inhibit Aβ neurotoxicity is of particular interest in the context of potential application of PrP analogues as therapeutic agents in AD. As a part of our attempt to synthesize m molecules able to interfere at the early stage of the Aβ’s aggregation process, we previously designed molecules bearing a known Aβ recognition group, namely the hydrophobic sequence KLVFF. In the present project, we aim to design and characterize new chemically functionalized peptide systems incorporating amino acid sequences from prion protein in addition to the KLVFF sequence (Prion/Aβ chimera peptides). The use of di-functional molecules, capable of synergic and/or additive actions to recognize different regions of the amyloid beta, represent a promising approaches for the development of new class of therapeutic agents for AD.