ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Role of presenilins in neuronal calcium homeostasis.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.
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Who cites it
110 citing papers in PubMed, 177 citations in OpenAlex.
- Calcium dysregulation in neurovascular function in Alzheimer's disease: mechanisms, therapeutic targets.GeroScience · 2026Review
- Calbindin-D28k deficiency mediates tau-driven hippocampal hyperexcitement and cognitive impairment.Translational neurodegeneration · 2026Article
- STIM Proteins: The Gas and Brake of Calcium Entry in Neurons.Neuroscience bulletin · 2025Review
- Sigma 1 Receptor and Its Pivotal Role in Neurological Disorders.ACS pharmacology & translational science · 2025Review
- Purinergic agonists increase [CaAmerican journal of physiology. Cell physiology · 2024Article
- Distinct calcium sources regulate temporal profiles of NMDAR and mGluR-mediated protein synthesis.Life science alliance · 2024Article
- Amygdala neuronal dyshomeostasis via 5-HT receptors mediates mood and cognitive defects in Alzheimer's disease.Aging cell · 2024Article
- Familial Alzheimer's Disease Neurons Bearing Mutations inLife (Basel, Switzerland) · 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
- Effects of Intranasal Dantrolene Nanoparticles on Brain Concentration and Behavior in PS19 Tau Transgenic Mice.Journal of Alzheimer's disease : JAD · 2024Article
- "Dirty Dancing" of Calcium and Autophagy in Alzheimer's Disease.Life (Basel, Switzerland) · 2023Review
- A Gating Mutation in Ryanodine Receptor Type 2 Rescues Phenotypes of Alzheimer's Disease Mouse Models by Upregulating Neuronal Autophagy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Regulation of Ryanodine Receptor-Dependent Neurotransmitter Release by AIP, Calstabins, and Presenilins.Advances in neurobiology · 2023Article
- The STIM1/2-Regulated Calcium Homeostasis Is Impaired in Hippocampal Neurons of the 5xFAD Mouse Model of Alzheimer's Disease.International journal of molecular sciences · 2022Article
- Neuronal hyperexcitability in Alzheimer's disease: what are the drivers behind this aberrant phenotype?Translational psychiatry · 2022Review
- Axonal transport of late endosomes and amphisomes is selectively modulated by local CaScience advances · 2022Article
- Aberrant miR-339-5p/neuronatin signaling causes prodromal neuronal calcium dyshomeostasis in mutant presenilin mice.The Journal of clinical investigation · 2022Article
- Oral nimodipine treatment has no effect on amyloid pathology or neuritic dystrophy in the 5XFAD mouse model of amyloidosis.PloS one · 2022Article
- Sigma receptors and neurological disorders.Pharmacological reports : PR · 2021Review
- Ryanodine Receptors: A Potential Treatment Target in Various Neurodegenerative Disease.Cellular and molecular neurobiology · 2021Review
50 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder. Familial AD (FAD) mutations in presenilins have been linked to calcium (Ca(2+)) signaling abnormalities. To explain these results, we previously proposed that presenilins function as endoplasmic reticulum (ER) passive Ca(2+) leak channels. To directly investigate the role of presenilins in neuronal ER Ca(2+) homeostasis, we here performed a series of Ca(2+) imaging experiments with primary neuronal cultures from conditional presenilin double-knock-out mice (PS1(dTAG/dTAG), PS2(-/-)) and from triple-transgenic AD mice (KI-PS1(M146V), Thy1-APP(KM670/671NL), Thy1-tau(P301L)). Obtained results provided additional support to the hypothesis that presenilins function as ER Ca(2+) leak channels in neurons. Interestingly, we discovered that presenilins play a major role in ER Ca(2+) leak function in hippocampal but not in striatal neurons. We further discovered that, in hippocampal neurons, loss of presenilin-mediated ER Ca(2+) leak function was compensated by an increase in expression and function of ryanodine receptors (RyanRs). Long-term feeding of the RyanR inhibitor dantrolene to amyloid precursor protein-presenilin-1 mice (Thy1-APP(KM670/671NL), Thy1-PS1(L166P)) resulted in an increased amyloid load, loss of synaptic markers, and neuronal atrophy in hippocampal and cortical regions. These results indicate that disruption of ER Ca(2+) leak function of presenilins may play an important role in AD pathogenesis.
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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.