ArticleThe Journal of biological chemistry2011
Presenilins promote the cellular uptake of copper and zinc and maintain copper chaperone of SOD1-dependent copper/zinc superoxide dismutase activity.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 74 citations in OpenAlex.
- Targeting Biometals in Alzheimer's Disease with Metal Chelating Agents Including Coumarin Derivatives.CNS drugs · 2024Review
- Review
- Recent Development in the Understanding of Molecular and Cellular Mechanisms Underlying the Etiopathogenesis of Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Aberrance of Zinc Metalloenzymes-Induced Human Diseases and Its Potential Mechanisms.Nutrients · 2021Review
- Molecular Mechanisms of Metal Toxicity in the Pathogenesis of Alzheimer's Disease.Molecular neurobiology · 2021Review
- Alzheimer risk factors age and female sex induce cortical Aβ aggregation by raising extracellular zinc.Molecular psychiatry · 2020Article
- Amyloids: Regulators of Metal Homeostasis in the Synapse.Molecules (Basel, Switzerland) · 2020Review
- Selenium and Zinc Biofortification ofMolecules (Basel, Switzerland) · 2020Article
- Exploring the Extended Biological Functions of the Human Copper Chaperone of Superoxide Dismutase 1.The protein journal · 2019Review
- Article
- A Sensitive, Nonradioactive Assay for Zn(II) Uptake into Metazoan Cells.Biochemistry · 2018Article
- Drosophila melanogaster Models of Metal-Related Human Diseases and Metal Toxicity.International journal of molecular sciences · 2017Review
- Lithium suppression of tau induces brain iron accumulation and neurodegeneration.Molecular psychiatry · 2017Article
- Biometal Dyshomeostasis and Toxic Metal Accumulations in the Development of Alzheimer's Disease.Frontiers in molecular neuroscience · 2017Review
- The Role of Presenilin in Protein Trafficking and Degradation-Implications for Metal Homeostasis.Journal of molecular neuroscience : MN · 2016Review
- Comparison of Metal Levels between Postmortem Brain and Ventricular Fluid in Alzheimer's Disease and Nondemented Elderly Controls.Toxicological sciences : an official journal of the Society of Toxicology · 2016Article
- Increased cortical expression of the zinc transporter SLC39A12 suggests a breakdown in zinc cellular homeostasis as part of the pathophysiology of schizophrenia.NPJ schizophrenia · 2016Article
- Biometals and their therapeutic implications in Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2015Review
- Deregulation of subcellular biometal homeostasis through loss of the metal transporter, Zip7, in a childhood neurodegenerative disorder.Acta neuropathologica communications · 2014Article
- Metals and cholesterol: two sides of the same coin in Alzheimer's disease pathology.Frontiers in aging neuroscience · 2014Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dyshomeostasis of extracellular zinc and copper has been implicated in β-amyloid aggregation, the major pathology associated with Alzheimer disease. Presenilin mediates the proteolytic cleavage of the β-amyloid precursor protein to release β-amyloid, and mutations in presenilin can cause familial Alzheimer disease. We tested whether presenilin expression affects copper and zinc transport. Studying murine embryonic fibroblasts (MEFs) from presenilin knock-out mice or RNA interference of presenilin expression in HEK293T cells, we observed a marked decrease in saturable uptake of radiolabeled copper and zinc. Measurement of basal metal levels in 6-month-old presenilin 1 heterozygous knock-out (PS1(+/-)) mice revealed significant deficiencies of copper and zinc in several tissues, including brain. Copper/zinc superoxide dismutase (SOD1) activity was significantly decreased in both presenilin knock-out MEFs and brain tissue of presenilin 1 heterozygous knock-out mice. In the MEFs and PS1(+/-) brains, copper chaperone of SOD1 (CCS) levels were decreased. Zinc-dependent alkaline phosphatase activity was not decreased in the PS null MEFs. These data indicate that presenilins are important for cellular copper and zinc turnover, influencing SOD1 activity, and having the potential to indirectly impact β-amyloid aggregation through metal ion clearance.
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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.