Potentiation of amyloid-ß peptide neurotoxicity in human dental-pulp neuron-like cells by the membrane lipid peroxidation product 4-hydroxynonenal.

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-ß peptide (Aß), whose excessive accumulation in specific brain areas is a hallmark of AD. Conversely, Aß production is up-regulated by this multifunctional aldehyde. Findings reported here point to the ability of HNE and Aß to interact, with consequent potentiation of Aß'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 Aß uptake and intracellular accumulation, by overexpressing two of the three components of the plasma membrane multireceptor complex CD36/CD47/ß1-integrin: experimental and clinical data indicate that intraneuronal accumulation of Aß is an early event possibly playing a primary role in AD pathogenesis. That HNE-mediated overexpression of CD36 and ß1-integrin, which plays a key role in HNE's potentiating Aß neurotoxicity, in terms of necrosis, was confirmed when this effect was prevented by specific antibodies against the two receptors.