b-Sheet aggregates and amyloid fibrils rising from conformational changes of proteins are observed in several pathological human conditions. These structures are organized in b-strands that can reciprocally interact by hydrophobic and p–p interactions. The amyloid aggregates can give rise to pathological conditions through complex biochemical mechanisms whose physico-chemical nature has been understood in recent times. This review focuses on the various classes of natural and synthetic small molecules able to act against b-amyloid fibrillogenesis and toxicity that may represent new pharmacological tools in Alzheimer’s diseases. Some peptides, named ‘b-sheet breaker peptides’, are able to hamper amyloid aggregation and fibrillogenesis by interfering with and destabilizing the non native b-sheet structures. Other natural compounds, like polyphenols or indolic molecules such as melatonin, can interfere with b-amyloid peptide pathogenicity by inhibiting aggregation and counteracting oxidative stress that is a key hallmark in Alzheimer’s disease.
b-Sheet interfering molecules acting against b-amyloid aggregation and fibrillogenesis / Francioso, Antonio; Punzi, Pasqualina; Boffi, Alberto; Lori, Clorinda; Martire, Sara; Giordano, CESARE GIOVANNI; D'Erme, Maria; Mosca, Luciana. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 1464-3391. - STAMPA. - 23:(2015), pp. 1671-1683. [10.1016/j.bmc.2015.02.041]