Title: Traffic-related air pollutants (TRAP-PM) promote neuronal amyloidogenesis through oxidative damage to lipid rafts.
Authors: Cacciottolo, Mafalda; Morgan, Todd E; Saffari, Arian A; Shirmohammadi, Farimah; Forman, Henry Jay; Sioutas, Costantinos; Finch, Caleb E
Published In Free Radic Biol Med, (2020 02 01)
Abstract: Traffic-related air pollution particulate matter (TRAP-PM) is associated with increased risk of Alzheimer Disease (AD). Rodent models respond to nano-sized TRAP-PM (nPM) with increased production of amyloid Aβ peptides, concurrently with oxidative damage. Because pro-Aβ processing of the amyloid precursor protein (APP) occurs on subcellular lipid rafts, we hypothesized that oxidative stress from nPM exposure would alter lipid rafts to favor Aβ production. This hypothesis was tested with J20 mice and N2a cells transgenic for hAPPswe (familial AD). Exposure of J20-APPswe mice to nPM for 150 h caused increased lipid oxidation (4-HNE) and increased the pro-amyloidogenic processing of APP in lipid raft fractions in cerebral cortex; the absence of these changes in cerebellum parallels the AD brain region selectivity for Aβ deposits. In vitro, nPM induced similar oxidative responses in N2a-APPswe cells, with dose-dependent production of NO, oxidative damage (4-HNE, 3NT), and lipid raft alterations of APP with increased Aβ peptides. The antioxidant N-acetyl-cysteine (NAC) attenuated nPM-induced oxidative damage and lipid raft alterations of APP processing. These findings identify neuronal lipid rafts as novel targets of oxidative damage in the pro-amyloidogenic effects of air pollution.
PubMed ID: 31883973
MeSH Terms: No MeSH terms associated with this publication