Combating Proteins with Proteins: Engineering Cell-Penetrating Peptide Antagonists of Amyloid-β Aggregation and Associated Neurotoxicity

A central event that underlies the etiology of Alzheimer's disease (AD) is the self-assembly of the amyloid-β (Aβ) peptide into aggregates termed amyloids. Increasing evidence implicates soluble prefibrillar Aβ oligomers in the neurodegeneration and synaptic dysfunction in AD. Recently we introduced a new class of highly promising antagonists of Aβ amyloidogenesis: designed cell-penetrating peptides (CPPs). These CPPs combine the attractive intrinsic properties of peptides (high target specificity and selectivity, biocompatibility, biodegradability, and ease and low cost of production) with potent therapeutic effects (inhibition of Aβ oligomerization, fiber formation, and neurotoxicity) and highly efficient delivery (to target cells and subcellular organelles).