ArticleThe FEBS journal2009
Interactions between the amyloid precursor protein C-terminal domain and G proteins mediate calcium dysregulation and amyloid beta toxicity in Alzheimer's disease.
Article in The FEBS journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Cell adhesion and intracellular calcium signaling in neurons.Cell communication and signaling : CCS · 2013Pooled it
- APP-C31 pathology as a target in neurodegenerative diseases.Journal of biomedical science · 2026Review
- Effect of Aβ Oligomers on Neuronal APP Triggers a Vicious Cycle Leading to the Propagation of Synaptic Plasticity Alterations to Healthy Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Role of endolysosomes and inter-organellar signaling in brain disease.Neurobiology of disease · 2020Review
- GFrontiers in aging neuroscience · 2019Review
- Amyloid Precursor Protein family as unconventional Go-coupled receptors and the control of neuronal motility.Neurogenesis (Austin, Tex.) · 2017Review
- Role of APP Interactions with Heterotrimeric G Proteins: Physiological Functions and Pathological Consequences.Frontiers in molecular neuroscience · 2017Review
- APP Receptor? To Be or Not To Be.Trends in pharmacological sciences · 2016Review
- Amyloid Precursor Proteins Are Dynamically Trafficked and Processed during Neuronal Development.Frontiers in molecular neuroscience · 2016Article
- Comparative analysis of single and combined APP/APLP knockouts reveals reduced spine density in APP-KO mice that is prevented by APPsα expression.Acta neuropathologica communications · 2014Article
- Amyloid precursor proteins interact with the heterotrimeric G protein Go in the control of neuronal migration.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- G proteins, p60TRP, and neurodegenerative diseases.Molecular neurobiology · 2013Review
- Relationships between the amyloid precursor protein and its various proteolytic fragments and neuronal systems.Alzheimer's research & therapy · 2012Article
- Novel GαS-protein signaling associated with membrane-tethered amyloid precursor protein intracellular domain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- P60TRP interferes with the GPCR/secretase pathway to mediate neuronal survival and synaptogenesis.Journal of cellular and molecular medicine · 2011Article
- Calcium signaling and amyloid toxicity in Alzheimer disease.The Journal of biological chemistry · 2010Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Alzheimer's disease is characterized by neuropathological accumulations of amyloid beta(1-42) [A beta(1-42)], a cleavage product of the amyloid precursor protein (APP). Recent studies have highlighted the role of APP in A beta-mediated toxicity and have implicated the G-protein system; however, the exact mechanisms underlying this pathway are as yet undetermined. In this context, we sought to investigate the role of calcium upregulation following APP-dependent, A beta-mediated G-protein activation. Initial studies on the interaction between APP, A beta and Go proteins demonstrated that the interaction between APP, specifically its C-terminal -YENPTY- region, and Go was reduced in the presence of A beta. Cell death and calcium influx in A beta-treated cells were shown to be APP dependent and to involve G-protein activation because these effects were blocked by use of the G-protein inhibitor, pertussis toxin. Collectively, these results highlight a role for the G-protein system in APP-dependent, A beta-induced toxicity and calcium dysregulation. Analysis of the APP:Go interaction in human brain samples from Alzheimer's disease patients at different stages of the disease revealed a decrease in the interaction, correlating with disease progression. Moreover, the reduced interaction between APP and Go was shown to correlate with an increase in membrane A beta levels and G-protein activity, showing for first time that the APP:Go interaction is present in humans and is responsive to A beta load. The results presented support a role for APP in A beta-induced G-protein activation and suggest a mechanism by which basal APP binding to Go is reduced under pathological loads of A beta, liberating Go and activating the G-protein system, which may in turn result in downstream effects including calcium dysregulation. These results also suggest that specific antagonists of G-protein activity may have a therapeutic relevance in Alzheimer's disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.