Β-Sheet interfering molecules acting against β-amyloid aggregation and fibrillogenesis. Issue 8 (15th April 2015)

• Record Type: Journal Article
• Authors: Francioso, Antonio; Punzi, Pasqualina; Boffi, Alberto; Lori, Clorinda; Martire, Sara; Giordano, Cesare; D'Erme, Maria; Mosca, Luciana
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 8(2015)
• Page Start: 1671
• Page End: 1683
• Publication Date: 2015-04-15
• Subjects: Alzheimer's disease -- Amyloid fibrillogenesis -- β-Sheet aggregates -- β-Sheet breaker peptides -- Natural compounds; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.02.041
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: β-Sheet aggregates and amyloid fibrils rising from conformational changes of proteins are observed in several pathological human conditions. These structures are organized in β-strands that can reciprocally interact by hydrophobic and π–π 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 β-amyloid fibrillogenesis and toxicity that may represent new pharmacological tools in Alzheimer's diseases. Some peptides, named 'β-sheet breaker peptides', are able to hamper amyloid aggregation and fibrillogenesis by interfering with and destabilizing the non native β-sheet structures. Other natural compounds, like polyphenols or indolic molecules such as melatonin, can interfere with β-amyloid peptide pathogenicity by inhibiting aggregation and counteracting oxidative stress that is a key hallmark in Alzheimer's disease.