ArticleInternational journal of Alzheimer's disease2010
Effect of Metal Chelators on γ-Secretase Indicates That Calcium and Magnesium Ions Facilitate Cleavage of Alzheimer Amyloid Precursor Substrate.
Article in International journal of Alzheimer's disease, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- The Aggravating Role of Failing Neuropeptide Networks in the Development of Sporadic Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Role of neurotoxicants in the pathogenesis of Alzheimer's disease: a mechanistic insight.Annals of medicine · 2021Review
- Molecular Mechanisms of Metal Toxicity in the Pathogenesis of Alzheimer's Disease.Molecular neurobiology · 2021Review
- Alterations of the Endoplasmic Reticulum (ER) Calcium Signaling Molecular Components in Alzheimer's Disease.Cells · 2020Review
- PRL-2 phosphatase is required for vascular morphogenesis and angiogenic signaling.Communications biology · 2020Article
- Reversal of Calcium Dysregulation as Potential Approach for Treating Alzheimer's Disease.Current Alzheimer research · 2020Review
- Metal Ion Effects on Aβ and Tau Aggregation.International journal of molecular sciences · 2018Review
- Amyloid β production is regulated by β2-adrenergic signaling-mediated post-translational modifications of the ryanodine receptor.The Journal of biological chemistry · 2017Article
- Biometal Dyshomeostasis and Toxic Metal Accumulations in the Development of Alzheimer's Disease.Frontiers in molecular neuroscience · 2017Review
- Metals and Neuronal Metal Binding Proteins Implicated in Alzheimer's Disease.Oxidative medicine and cellular longevity · 2016Review
- Identification of tetrahydrocarbazoles as novel multifactorial drug candidates for treatment of Alzheimer's disease.Translational psychiatry · 2014Article
- Risk of new-onset atrial fibrillation in elderly patients with the overlap syndrome: a retrospective cohort study.Journal of geriatric cardiology : JGC · 2013Article
- Article
- Augmented generation of protein fragments during wakefulness as the molecular cause of sleep: a hypothesis.Protein science : a publication of the Protein Society · 2012Article
- Ryanodine receptor blockade reduces amyloid-β load and memory impairments in Tg2576 mouse model of Alzheimer disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- New therapeutic targets in Alzheimer's disease: brain deregulation of calcium and zinc.Cell death & disease · 2011Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gamma-secretase is involved in the production of Aβ amyloid peptides. It cleaves the transmembrane domain of the amyloid precursor protein (APP) at alternative sites to produce Aβ and the APP intracellular domain (AICD). Metal ions play an important role in Aβ aggregation and metabolism, thus metal chelators and ligands represent potential therapeutic agents for AD treatment. A direct effect of metal chelators on γ-secretase has not yet been investigated. The authors used an in vitro γ-secretase assay consisting of cleavage of APP C100-3XFLAG by endogenous γ-secretase from rodent brains and human neuroblastoma SH-SY5Y, and detected AICD production by western blotting. Adding metalloprotease inhibitors to the reaction showed that clioquinol, phosphoramidon, and zinc metalloprotease inhibitors had no significant effect on γ-secretase activity. In contrast, phenanthroline, EDTA, and EGTA markedly decreased γ-secretase activity that could be restored by adding back calcium and magnesium ions. Mg(2+) stabilized a 1,000 kDa presenilin 1 complex through blue native gel electrophoresis and size-exclusion chromatography. Data suggest that Ca(2+) and Mg(2+) stabilize γ-secretase and enhance its activity.
Identifiers
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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.