title: Polyamine Conjugation as a Promising Strategy To Target Amyloid Aggregation in the Framework of Alzheimer's Disease.
abstract: Spermine conjugates2-6, carrying variously decorated 3,5-dibenzylidenepiperidin-4-one as bioactive motives, were designed to direct antiaggregating properties into mitochondria, using a polyamine functionality as the vehicle tool. The study confirmed mitochondrial import of the catechol derivative2, which displayed effective antiaggregating activity and neuroprotective effects against Aβ-induced toxicity. Notably, a key functional role for the polyamine motif in Aβ molecular recognition was also unraveled. This experimental readout, which was supported by in silico studies, gives important new insight into the polyamine's action. Hence, we propose polyamine conjugation as a promising strategy for the development of neuroprotectant leads that may contribute to decipher the complex picture of Aβ toxicity.
authors.affiliation: Department of Pharmacy & Biotechnology, Alma Mater Studiorum-University of Bologna , Via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Simoni
authors.affiliation: Department of Pharmacy & Biotechnology, Alma Mater Studiorum-University of Bologna , Via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Caporaso
authors.affiliation: Department of Pharmacy & Biotechnology, Alma Mater Studiorum-University of Bologna , Via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Christian
authors.initials: C
authors.lastname: Bergamini
authors.affiliation: Department of Pharmacy & Biotechnology, Alma Mater Studiorum-University of Bologna , Via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Jessica
authors.initials: J
authors.lastname: Fiori
authors.affiliation: Department of Pharmacy & Biotechnology, Alma Mater Studiorum-University of Bologna , Via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Romana
authors.initials: R
authors.lastname: Fato
authors.affiliation: Faculty of Chemistry, Biological & Chemical Research Centre University of Warsaw , Pasteura 1, 02093 Warsaw, Poland.
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Miszta
authors.affiliation: Faculty of Chemistry, Biological & Chemical Research Centre University of Warsaw , Pasteura 1, 02093 Warsaw, Poland.
authors.forename: Sławomir
authors.initials: S
authors.lastname: Filipek
authors.affiliation: IRCCS Associazione Oasi Maria S.S., Institute for Research on Mental Retardation and Brain Aging, Via Conte Ruggero 73, 94018 Troina, Enna, Italy; Department of Drug Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Caraci
authors.affiliation: Institute of Biostructure and Bioimaging, National Research Council (CNR) , Via P. Gaifami 18, 95126 Catania, Italy.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Giuffrida
authors.affiliation: Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna , Corso D'Augusto 237, 47921 Rimini, Italy.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Andrisano
authors.affiliation: Department of Pharmacy & Biotechnology, Alma Mater Studiorum-University of Bologna , Via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Minarini
authors.affiliation: Department of Pharmacy & Biotechnology, Alma Mater Studiorum-University of Bologna , Via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Bartolini
authors.affiliation: Department of Pharmacy & Biotechnology, Alma Mater Studiorum-University of Bologna , Via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Rosini
keywords: Alzheimer’s disease; amyloid; mitochondria; polyamines