title: β-sheet interfering molecules acting against β-amyloid aggregation and fibrillogenesis.
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.
authors.affiliation: Department of Biochemistry, Sapienza University of Rome, p.le Aldo Moro 5, 00185 Roma, Italy. Electronic address: antonio.francioso@uniroma1.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Francioso
authors.affiliation: Department of Chemistry, Sapienza University of Rome, p.le Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Pasqualina
authors.initials: P
authors.lastname: Punzi
authors.affiliation: Department of Biochemistry, Sapienza University of Rome, p.le Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Boffi
authors.affiliation: Department of Biochemistry, Sapienza University of Rome, p.le Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Clorinda
authors.initials: C
authors.lastname: Lori
authors.affiliation: Department of Biochemistry, Sapienza University of Rome, p.le Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Martire
authors.affiliation: Biomolecular Chemistry Institute, National Council of Research, p.le Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Giordano
authors.affiliation: Department of Biochemistry, Sapienza University of Rome, p.le Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: D'Erme
authors.affiliation: Department of Biochemistry, Sapienza University of Rome, p.le Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Mosca
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D059808:Polyphenols / Q000737:chemistry / Q000494:pharmacology; D066329:Protein Aggregates / Q000187:drug effects; D066263:Protein Aggregation, Pathological / Q000188:drug therapy* / Q000378:metabolism; D017433:Protein Structure, Secondary / Q000187:drug effects*
chemical_list: D016229:Amyloid beta-Peptides; D001688:Biological Products; D010455:Peptides; D059808:Polyphenols; D066329:Protein Aggregates
keywords: Alzheimer’s disease; Amyloid fibrillogenesis; Natural compounds; β-Sheet aggregates; β-Sheet breaker peptides