Rationally Designed Peptoid Inhibitors of Amyloid-β Oligomerization.

While plaques comprised of fibrillar Aβ aggregates are hallmarks of Alzheimer's disease, soluble Aβ oligomers present higher neurotoxicity. Thus, one therapeutic approach is to prevent the formation of Aβ oligomers and reduce their associated harmful effects. We have proposed a peptoid mimic of the Aβ hydrophobic KLVFF core as an ideal candidate aggregation inhibitor due to its ability to evade proteolytic degradation via repositioning of the side chain from the α-carbon to the amide nitrogen.

Modulating the RAGE-Induced Inflammatory Response: Peptoids as RAGE Antagonists.

While the primary pathology of Alzheimer's disease (AD) is defined by brain deposition of amyloid-β (Aβ) plaques and tau neurofibrillary tangles, chronic inflammation has emerged as an important factor in AD etiology. Upregulated cell surface expression of the receptor for advanced glycation end-products (RAGE), a key receptor of innate immune response, is reported in AD. In parallel, RAGE ligands, including Aβ aggregates, HMGB1, and S100B, are elevated in AD brain.