ArticleNeurobiology of disease2012
Amyloid precursor proteins are protective in Drosophila models of progressive neurodegeneration.
Article in Neurobiology of disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 47 citations in OpenAlex.
- Lipofuscin accumulation in aging and neurodegeneration: a potential "timebomb" overlooked in Alzheimer's disease.Translational neurodegeneration · 2025Review
- A large-scale in vivo screen to investigate the roles of human genes in Drosophila melanogaster.G3 (Bethesda, Md.) · 2024Article
- The amyloid precursor protein intracellular domain induces sleep disruptions and its nuclear localization fluctuates in circadian pacemaker neurons in Drosophila and mice.Neurobiology of disease · 2024Article
- Integrative analysis reveals a conserved role for the amyloid precursor protein in proteostasis during aging.Nature communications · 2023Article
- Knockdown of Amyloid Precursor Protein: Biological Consequences and Clinical Opportunities.Frontiers in neuroscience · 2022Review
- The Drosophila amyloid precursor protein homologue mediates neuronal survival and neuroglial interactions.PLoS biology · 2020Article
- Drosophila Full-Length Amyloid Precursor Protein Is Required for Visual Working Memory and Prevents Age-Related Memory Impairment.Current biology : CB · 2018Article
- Article
- UsingBioMed research international · 2018Review
- Role of APP Interactions with Heterotrimeric G Proteins: Physiological Functions and Pathological Consequences.Frontiers in molecular neuroscience · 2017Review
- Neuronal migration during development and the amyloid precursor protein.Current opinion in insect science · 2016Review
- Amyloid Precursor Proteins Are Dynamically Trafficked and Processed during Neuronal Development.Frontiers in molecular neuroscience · 2016Article
- Analysis of Amyloid Precursor Protein Function in Drosophila melanogaster.Frontiers in molecular neuroscience · 2016Review
- Role ofFrontiers in molecular neuroscience · 2016Review
- The APP Intracellular Domain Is Required for Normal Synaptic Morphology, Synaptic Plasticity, and Hippocampus-Dependent Behavior.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Modeling the complex pathology of Alzheimer's disease in Drosophila.Experimental neurology · 2015Review
- Manipulations of amyloid precursor protein cleavage disrupt the circadian clock in aging Drosophila.Neurobiology of disease · 2015Article
- The full-length form of the Drosophila amyloid precursor protein is involved in memory formation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Chronic low-level domoic acid exposure alters gene transcription and impairs mitochondrial function in the CNS.Aquatic toxicology (Amsterdam, Netherlands) · 2014Article
- Holo-APP and G-protein-mediated signaling are required for sAPPα-induced activation of the Akt survival pathway.Cell death & disease · 2014Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The processing of Amyloid Precursor Proteins (APPs) results in several fragments, including soluble N-terminal ectodomains (sAPPs) and C-terminal intracellular domains (AICD). sAPPs have been ascribed neurotrophic or neuroprotective functions in cell culture, although β-cleaved sAPPs can have deleterious effects and trigger neuronal cell death. Here we describe a neuroproprotective function of APP and fly APPL (Amyloid Precursor Protein-like) in vivo in several Drosophila mutants with progressive neurodegeneration. We show that expression of the N-terminal ectodomain is sufficient to suppress the progressive degeneration in these mutants and that the secretion of the ectodomain is required for this function. In addition, a protective effect is achieved by expressing kuzbanian (which has α-secretase activity) whereas expression of fly and human BACE aggravates the phenotypes, suggesting that the protective function is specifically mediated by the α-cleaved ectodomain. Furthermore, genetic and molecular studies suggest that the N-terminal fragments interact with full-length APPL activating a downstream signaling pathway via the AICD. Because we show protective effects in mutants that affect different genes (AMP-activated protein kinase, MAP1b, rasGAP), we propose that the protective effect is not due to a genetic interaction between APPL and these genes but a more general aspect of APP proteins. The result that APP proteins and specifically their soluble α-cleaved ectodomains can protect against progressive neurodegeneration in vivo provides support for the hypothesis that a disruption of the physiological function of APP could play a role in the pathogenesis of Alzheimer's Disease.
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