title: Small molecules interacting with α-synuclein: antiaggregating and cytoprotective properties.
abstract: Curcumin, a dietary polyphenol, has shown a potential to act on the symptoms of neurodegenerative disorders, including Alzheimer's and Parkinson's diseases, as a consequence of its antioxidant, anti-inflammatory and anti-protein aggregation properties. Unfortunately, curcumin undergoes rapid degradation at physiological pH into ferulic acid, vanillin and dehydrozingerone, making it an unlikely drug candidate. Here, we evaluated the ability of some curcumin by-products: dehydrozingerone (1), its O-methyl derivative (2), zingerone (3), and their biphenyl analogues (4-6) to interact with α-synuclein (AS), using CD and fluorescence spectroscopy. In addition, the antioxidant properties and the cytoprotective effects in rat pheochromocytoma (PC12) cells prior to intoxication with H2O2, MPP+ and MnCl2 were examined while the Congo red assay was used to evaluate the ability of these compounds to prevent aggregation of AS. We found that the biphenyl zingerone analogue (6) interacts with high affinity with AS and also displays the best antioxidant properties while the biphenyl analogues of dehydrozingerone (4) and of O-methyl-dehydrozingerone (5) are able to partially inhibit the aggregation process of AS, suggesting the potential role of a hydroxylated biphenyl scaffold in the design of AS aggregation inhibitors.
authors: Institute of Biomolecular Chemistry of CNR, Padua, Italy.
authors: Anna
authors: A
authors: Marchiani
authors: Stefano
authors: S
authors: Mammi
authors: Giuliano
authors: G
authors: Siligardi
authors: Rohanah
authors: R
authors: Hussain
authors: Isabella
authors: I
authors: Tessari
authors: Luigi
authors: L
authors: Bubacco
authors: Giovanna
authors: G
authors: Delogu
authors: Davide
authors: D
authors: Fabbri
authors: Maria A
authors: MA
authors: Dettori
authors: Daniele
authors: D
authors: Sanna
authors: Sonia
authors: S
authors: Dedola
authors: Pier A
authors: PA
authors: Serra
authors: Paolo
authors: P
authors: Ruzza
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D003474:Curcumin / Q000031:analogs & derivatives* / Q000378:metabolism*; D019610:Cytoprotection / Q000187:drug effects; D006139:Guaiacol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism; D010673:Pheochromocytoma / Q000378:metabolism; D051381:Rats; D013343:Styrenes / Q000737:chemistry / Q000378:metabolism*; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D013343:Styrenes; D051844:alpha-Synuclein; C013738:zingerone; D006139:Guaiacol; C052933:methyl-3-methoxy-4-hydroxystyryl ketone; D003474:Curcumin