ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
UV irradiation accelerates amyloid precursor protein (APP) processing and disrupts APP axonal transport.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 31 citations in OpenAlex.
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- Heads Up! Interlinked Amyloidogenic and Axonal Transport Pathways in Concussion-Induced Neurodegeneration.Neuroscience insights · 2022Article
- Amyloidogenic Processing of Amyloid Precursor Protein Drives Stretch-Induced Disruption of Axonal Transport in hiPSC-Derived Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Kinesin-1-mediated axonal transport of CB1 receptors is required for cannabinoid-dependent axonal growth and guidance.Development (Cambridge, England) · 2020Article
- Molecular basis for dyneinopathies reveals insight into dynein regulation and dysfunction.eLife · 2019Article
- Excess active P13K rescues huntingtin-mediated neuronal cell death but has no effect on axonal transport defects.Apoptosis : an international journal on programmed cell death · 2019Article
- Mechanisms of Toxicity of Industrially Relevant Silicomanganese Dust on Human 1321N1 Astrocytoma Cells: An In Vitro Study.International journal of molecular sciences · 2019Article
- Cellular Responses of Industrially Relevant Silica Dust on Human Glial Cells In Vitro.International journal of molecular sciences · 2019Article
- A Role forFrontiers in cellular neuroscience · 2019Article
- Full-length amyloid precursor protein regulates lipoprotein metabolism and amyloid-β clearance in human astrocytes.The Journal of biological chemistry · 2018Article
- Ethanol stimulates the in vivo axonal movement of neuropeptide dense-core vesicles in Drosophila motor neurons.Journal of neurochemistry · 2018Article
- Cytoplasmic fragment of Alcadein α generated by regulated intramembrane proteolysis enhances amyloid β-protein precursor (APP) transport into the late secretory pathway and facilitates APP cleavage.The Journal of biological chemistry · 2015Article
- Bidirectional cargo transport: moving beyond tug of war.Nature reviews. Molecular cell biology · 2014Review
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Overexpression and/or abnormal cleavage of amyloid precursor protein (APP) are linked to Alzheimer's disease (AD) development and progression. However, the molecular mechanisms regulating cellular levels of APP or its processing, and the physiological and pathological consequences of altered processing are not well understood. Here, using mouse and human cells, we found that neuronal damage induced by UV irradiation leads to specific APP, APLP1, and APLP2 decline by accelerating their secretase-dependent processing. Pharmacological inhibition of endosomal/lysosomal activity partially protects UV-induced APP processing implying contribution of the endosomal and/or lysosomal compartments in this process. We found that a biological consequence of UV-induced γ-secretase processing of APP is impairment of APP axonal transport. To probe the functional consequences of impaired APP axonal transport, we isolated and analyzed presumptive APP-containing axonal transport vesicles from mouse cortical synaptosomes using electron microscopy, biochemical, and mass spectrometry analyses. We identified a population of morphologically heterogeneous organelles that contains APP, the secretase machinery, molecular motors, and previously proposed and new residents of APP vesicles. These possible cargoes are enriched in proteins whose dysfunction could contribute to neuronal malfunction and diseases of the nervous system including AD. Together, these results suggest that damage-induced APP processing might impair APP axonal transport, which could result in failure of synaptic maintenance and neuronal dysfunction.
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Registered trials
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