title: Potentiation of amyloid-β peptide neurotoxicity in human dental-pulp neuron-like cells by the membrane lipid peroxidation product 4-hydroxynonenal.
abstract: Lipid peroxidation is generally considered as primarily implicated in the pathogenesis of Alzheimer's disease (AD); one of its more reactive end products, 4-hydroxynonenal (HNE), has been shown to cause neuron dysfunction and degeneration. HNE production in the brain is stimulated by the amyloid-β peptide (Aβ), whose excessive accumulation in specific brain areas is a hallmark of AD. Conversely, Aβ production is up-regulated by this multifunctional aldehyde. Findings reported here point to the ability of HNE and Aβ to interact, with consequent potentiation of Aβ's cytotoxicity as determined in vitro using neuron-like cells derived from human dental-pulp progenitor cells. Preincubation of cells with the aldehyde markedly up-regulated Aβ uptake and intracellular accumulation, by overexpressing two of the three components of the plasma membrane multireceptor complex CD36/CD47/β1-integrin: experimental and clinical data indicate that intraneuronal accumulation of Aβ is an early event possibly playing a primary role in AD pathogenesis. That HNE-mediated overexpression of CD36 and β1-integrin, which plays a key role in HNE's potentiating Aβ neurotoxicity, in terms of necrosis, was confirmed when this effect was prevented by specific antibodies against the two receptors.
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Orbassano, Turin, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Testa
authors.forename: Paola
authors.initials: P
authors.lastname: Gamba
authors.forename: Federica
authors.initials: F
authors.lastname: Di Scipio
authors.forename: Andrea Elio
authors.initials: AE
authors.lastname: Sprio
authors.forename: Paolina
authors.initials: P
authors.lastname: Salamone
authors.forename: Simona
authors.initials: S
authors.lastname: Gargiulo
authors.forename: Barbara
authors.initials: B
authors.lastname: Sottero
authors.forename: Fiorella
authors.initials: F
authors.lastname: Biasi
authors.forename: Giovanni Nicolao
authors.initials: GN
authors.lastname: Berta
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Poli
authors.forename: Gabriella
authors.initials: G
authors.lastname: Leonarduzzi
mesh_terms: D000328:Adult; D000447:Aldehydes / Q000494:pharmacology*; D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D000943:Antigens, Differentiation / Q000378:metabolism; D017209:Apoptosis; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D051928:CD47 Antigen / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D053144:Cell Nucleus Shape / Q000187:drug effects; D048430:Cell Shape; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation; D008563:Membrane Lipids / Q000378:metabolism; D009336:Necrosis; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D061251:Primary Cell Culture; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000447:Aldehydes; D016229:Amyloid beta-Peptides; D000943:Antigens, Differentiation; D018955:CD36 Antigens; D051928:CD47 Antigen; C497894:CD47 protein, human; D019012:Integrin beta1; D008563:Membrane Lipids; D007770:L-Lactate Dehydrogenase; C027576:4-hydroxy-2-nonenal