title: Diphenyl-diselenide suppresses amyloid-β peptide in Caenorhabditis elegans model of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is the most common and devastating neurodegenerative disease. The etiology of AD has yet to be fully understood, and common treatments remain largely non-efficacious. The amyloid hypothesis posits that extracellular amyloid-β (Aβ) deposits are the fundamental etiological factor of the disease. The present study tested the organoselenium compound diphenyl-diselenide (PhSe)2, which is characterized by its antioxidant and antiinflammatory properties and has shown efficacy in several neurodegenerative disease models. We employed a transgenic Caenorhabditis elegans AD model to analyze the effects of (PhSe)2 treatment on Aβ peptide-induced toxicity. Chronic exposure to (PhSe)2 attenuated oxidative stress induced by Aβ1-42, with concomitant recovery of associative learning memory in C. elegans. Additionally, (PhSe)2 decreased Aβ1-42 transgene expression, suppressed Aβ1-42 peptide, and downregulated hsp-16.2 by reducing the need for this chaperone under Aβ1-42-induced toxicity. These observations suggest that (PhSe)2 plays an important role in protecting against oxidative stress-induced toxicity, thus representing a promising pharmaceutical modality that attenuates Aβ1-42 expression.
authors.affiliation: Centro de Ciências Naturais e Exatas, Departamento de Química, Programa de Pós-graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: D C
authors.initials: DC
authors.lastname: Zamberlan
authors.affiliation: Centro de Ciências Naturais e Exatas, Departamento de Química, Programa de Pós-graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: L P
authors.initials: LP
authors.lastname: Arantes
authors.affiliation: Centro de Ciências Naturais e Exatas, Departamento de Química, Programa de Pós-graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: M L
authors.initials: ML
authors.lastname: Machado
authors.affiliation: Centro de Ciências Naturais e exatas, Ciência Viva, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: Golombieski
authors.affiliation: Centro de Ciências Naturais e Exatas, Departamento de Química, Programa de Pós-graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil. Electronic address: felix@ufsm.br.
authors.forename: F A A
authors.initials: FA
authors.lastname: Soares
mesh_terms: D000448:Aldicarb / Q000494:pharmacology; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D000975:Antioxidants / Q000008:administration & dosage*; D001245:Association Learning / Q000187:drug effects; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D006360:Heat-Shock Proteins / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D016566:Organoselenium Compounds / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D029742:Caenorhabditis elegans Proteins; D002800:Cholinesterase Inhibitors; D006360:Heat-Shock Proteins; D016566:Organoselenium Compounds; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C108431:hsp-16.2 protein, C elegans; D000448:Aldicarb
keywords: Alzheimer’s disease; C. elegans; amyloid-β; neurodegenerative diseases; selenium compounds