title: Multitarget strategies in Alzheimer's disease: benefits and challenges on the road to therapeutics.
abstract: Alzheimer's disease is a multifactorial syndrome, for which effective cures are urgently needed. Seeking for enhanced therapeutic efficacy, multitarget drugs have been increasingly sought after over the last decades. They offer the attractive prospect of tackling intricate network effects, but with the benefits of a single-molecule therapy. Herein, we highlight relevant progress in the field, focusing on acetylcholinesterase inhibition and amyloid pathways as two pivotal features in multitarget design strategies. We also discuss the intertwined relationship between selected molecular targets and give a brief glimpse into the power of multitarget agents as pharmacological probes of Alzheimer's disease molecular mechanisms.
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
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: Anna
authors.initials: A
authors.lastname: Minarini
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000077265:Donepezil; D055808:Drug Discovery; D005702:Galantamine / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007189:Indans / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D058990:Molecular Targeted Therapy; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000068836:Rivastigmine / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D013329:Structure-Activity Relationship
chemical_list: D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D005702:Galantamine; D000077265:Donepezil; D000068836:Rivastigmine
keywords: AChE inhibitors; Alzheimer's disease; acetylcholinesterase; amyloid-β; multitarget drugs; polypharmacology