Dataset Information

Traffic-related air pollutants (TRAP-PM) promote neuronal amyloidogenesis through oxidative damage to lipid rafts.

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.

SUBMITTER: Cacciottolo M

PROVIDER: S-EPMC7075030 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Traffic-related air pollutants (TRAP-PM) promote neuronal amyloidogenesis through oxidative damage to lipid rafts.

Cacciottolo Mafalda M Morgan Todd E TE Saffari Arian A AA Shirmohammadi Farimah F Forman Henry Jay HJ Sioutas Costantinos C Finch Caleb E CE

Free radical biology & medicine 20191226

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 ...[more]

PMID: 31883973

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Dataset Information

Traffic-related air pollutants (TRAP-PM) promote neuronal amyloidogenesis through oxidative damage to lipid rafts.

Publications

Traffic-related air pollutants (TRAP-PM) promote neuronal amyloidogenesis through oxidative damage to lipid rafts.

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