ArticleJournal of neurochemistry2009
Enhanced generation of Alzheimer's amyloid-beta following chronic exposure to phorbol ester correlates with differential effects on alpha and epsilon isozymes of protein kinase C.
Article in Journal of neurochemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- Revisiting APP secretases: an overview on the holistic effects of retinoic acid receptor stimulation in APP processing.Cellular and molecular life sciences : CMLS · 2022Review
- APP Binds to the EGFR Ligands HB-EGF and EGF, Acting Synergistically with EGF to Promote ERK Signaling and Neuritogenesis.Molecular neurobiology · 2021Article
- Sexual dimorphism in predisposition to Alzheimer's disease.Neurobiology of aging · 2018Review
- Inhibition of PKCδ reduces amyloid-β levels and reverses Alzheimer disease phenotypes.The Journal of experimental medicine · 2018Article
- Sex differences in chronic stress responses and Alzheimer's disease.Neurobiology of stress · 2018Review
- Atypical PKC, PKCλ/ι, activates β-secretase and increases AβNeurobiology of aging · 2018Article
- Gain-of-function mutations in protein kinase Cα (PKCα) may promote synaptic defects in Alzheimer's disease.Science signaling · 2016Article
- Inflammatory Eicosanoids Increase Amyloid Precursor Protein Expression via Activation of Multiple Neuronal Receptors.Scientific reports · 2015Article
- Effects of corticotrophin-releasing factor receptor 1 antagonists on amyloid-β and behavior in Tg2576 mice.Psychopharmacology · 2014Article
- Glutamate system, amyloid ß peptides and tau protein: functional interrelationships and relevance to Alzheimer disease pathology.Journal of psychiatry & neuroscience : JPN · 2013Review
- Bryostatin-1 vs. TPPB: dose-dependent APP processing and PKC-α, -δ, and -ε isoform activation in SH-SY5Y neuronal cells.Journal of molecular neuroscience : MN · 2012Article
- Corticotrophin releasing factor accelerates neuropathology and cognitive decline in a mouse model of Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2012Article
- The role of G protein-coupled receptors in the pathology of Alzheimer's disease.Nature reviews. Neuroscience · 2011Review
- Protein kinase C-regulated aβ production and clearance.International journal of Alzheimer's disease · 2011Article
- Retrieval of the Alzheimer's amyloid precursor protein from the endosome to the TGN is S655 phosphorylation state-dependent and retromer-mediated.Molecular neurodegeneration · 2010Article
- Reduction of beta-amyloid levels by novel protein kinase C(epsilon) activators.The Journal of biological chemistry · 2009Article
- Alphabeta hinders nuclear targeting of AICD and Fe65 in primary neuronal cultures.Journal of molecular neuroscience : MN · 2009Article
- S655 phosphorylation enhances APP secretory traffic.Molecular and cellular biochemistry · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Alzheimer's amyloid precursor protein (APP) sorting and processing are modulated through signal transduction mechanisms regulated by protein phosphorylation. Notably, protein kinase C (PKC) appears to be an important component in signaling pathways that control APP metabolism. PKCs exist in at least 11 conventional and unconventional isoforms, and PKCalpha and PKCepsilon isoforms have been specifically implicated in controlling the generation of soluble APP and amyloid-beta (Abeta) fragments of APP, although identification of the PKC substrate phospho-state-sensitive effector proteins remains challenging. In the current study, we present evidence that chronic application of phorbol esters to cultured cells in serum-free medium is associated with several phenomena, namely: (i) PKCalpha down-regulation; (ii) PKCepsilon up-regulation; (iii) accumulation of APP and/or APP carboxyl-terminal fragments in the trans Golgi network; (iv) disappearance of fluorescence from cytoplasmic vesicles bearing a green fluorescent protein tagged form of APP; (v) insensitivity of soluble APP release following acute additional phorbol application; and (vi) elevated cellular APP mRNA levels and holoprotein, and secreted Abeta. These data indicate that, unlike acute phorbol ester application, which is accompanied by lowered Abeta generation, chronic phorbol ester treatment causes differential regulation of PKC isozymes and increased Abeta generation. These data have implications for the design of amyloid-lowering strategies based on modulating PKC activity.
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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.