ArticleProceedings of the National Academy of Sciences of the United States of America2013
Presenilins regulate calcium homeostasis and presynaptic function via ryanodine receptors in hippocampal neurons.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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70 citing papers in PubMed, 117 citations in OpenAlex.
- Clustering Properties of Neuronal Ryanodine Receptor 2 and Remodeling in the APP/PS1 Mouse Model of Alzheimer's Disease.Acta physiologica (Oxford, England) · 2026Article
- Presenilin Loss Impairs Synaptic Transmission and Causes Axonal Degeneration through Ryanodine Receptor Dysfunction, Independent of γ-Secretase Activity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Dysferlin Protein-Protein Interaction Pathways in the Organ of Corti and Spiral Ganglion Intersect with Alzheimer's Protein Pathways.International journal of molecular sciences · 2025Article
- Presenilins as hub proteins controlling the endocytic and autophagic pathways and small extracellular vesicle secretion.Journal of extracellular vesicles · 2025Article
- Altered expression of Presenilin2 impacts endolysosomal homeostasis and synapse function in Alzheimer's disease-relevant brain circuits.Nature communications · 2024Article
- Pathophysiologic abnormalities in transgenic mice carrying the Alzheimer disease PSEN1 Δ440 mutation.Human molecular genetics · 2024Article
- Sexual dimorphism, altered hippocampal glutamatergic neurotransmission, and cognitive impairment in APP knock-in mice.Journal of Alzheimer's disease : JAD · 2024Article
- Cortical neurodegeneration caused byProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Distinct calcium sources regulate temporal profiles of NMDAR and mGluR-mediated protein synthesis.Life science alliance · 2024Article
- Lipophorin receptors genetically modulate neurodegeneration caused by reduction of Psn expression in the aging Drosophila brain.Genetics · 2024Article
- Cultured Rat Hippocampal Neurons Exposed to the Mitochondrial Uncoupler Carbonyl Cyanide Chlorophenylhydrazone Undergo a Rapid, Presenilin-Dependent Change in Neuronal Properties.International journal of molecular sciences · 2024Article
- Article
- Human Presenilin-1 delivered by AAV9 rescues impaired γ-secretase activity, memory deficits, and neurodegeneration inProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Developing a Gene Therapy for the Treatment of Autosomal Dominant Alzheimer's Disease.Human gene therapy · 2023Article
- Neuroprotective properties of anti-apoptotic BCL-2 proteins in 5xFAD mouse model of Alzheimer's disease.IBRO neuroscience reports · 2023Article
- Presenilins regulate synaptic plasticity in the perforant pathways of the hippocampus.Molecular brain · 2023Article
- Roles and Sources of Calcium in Synaptic Exocytosis.Advances in neurobiology · 2023Article
- TheArchives of medical science : AMS · 2023Article
- Regulation of Ryanodine Receptor-Dependent Neurotransmitter Release by AIP, Calstabins, and Presenilins.Advances in neurobiology · 2023Article
- Age-related Loss of miR-124 Causes Cognitive DeficitsAging and disease · 2022Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Presenilin (PS) plays a central role in the pathogenesis of Alzheimer's disease, and loss of PS causes progressive memory impairment and age-related neurodegeneration in the mouse cerebral cortex. In hippocampal neurons, PS is essential for neurotransmitter release, NMDA receptor-mediated responses, and long-term potentiation. PS is also involved in the regulation of calcium homeostasis, although the precise site of its action is less clear. Here we investigate the mechanism by which PS regulates synaptic function and calcium homeostasis using acute hippocampal slices from PS conditional knockout mice and primary cultured postnatal hippocampal neurons, in which PS is inducibly inactivated. Using two different calcium probes, Fura-2 and Mag-Fura-2, we found that inactivation of PS in primary hippocampal neurons does not affect calcium concentration in the endoplasmic reticulum. Rather, in the absence of PS, levels of ryanodine receptor (RyR) are reduced in the hippocampus, measured by Western analysis and radioligand binding assay, although the mRNA expression is unaffected. RyR-mediated function is also impaired, as indicated by reduced RyR agonist-induced calcium release from the ER and RyR-mediated synaptic responses in the absence of PS. Furthermore, knockdown of RyR expression in wild-type hippocampal neurons by two independent shRNAs to levels comparable with the RyR protein reduction in PS-deficient hippocampal neurons mimics the defects exhibited in calcium homeostasis and presynaptic function. Collectively, our findings show that PS regulates calcium homeostasis and synaptic function via RyR and suggest that disruption of intracellular calcium homeostasis may be an early pathogenic event leading to presynaptic dysfunction in Alzheimer's disease.
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