ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2004
Dysregulated IP3 signaling in cortical neurons of knock-in mice expressing an Alzheimer's-linked mutation in presenilin1 results in exaggerated Ca2+ signals and altered membrane excitability.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers, 1 of them a synthesis that pooled it.
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Who cites it
145 citing papers in PubMed, 1 synthesis or guideline pooled it, 273 citations in OpenAlex.
- Inter-organellar Communication in Parkinson's and Alzheimer's Disease: Looking Beyond Endoplasmic Reticulum-Mitochondria Contact Sites.Frontiers in neuroscience · 2022Pooled it
- Genetic ablation of neuronal mitochondrial calcium uptake impedes Alzheimer's disease progression.The EMBO journal · 2026Article
- The diverse forms and roles of the neuronal endoplasmic reticulum.Nature reviews. Neuroscience · 2026Review
- Neuronal Calcium Signaling and Cytoskeletal Dynamics in Neurodegeneration.International journal of molecular sciences · 2026Review
- Inflammatory mechanisms underlying early Alzheimer's disease pathology: evidence from the aging rhesus macaque brain.Frontiers in cellular neuroscience · 2026Review
- Abnormal calcium activity and CREB phosphorylation are associated with motor memory impairment in presenilin-1 mutant knock-in mice.Cell calcium · 2025Article
- The roles of mitochondria in global and local intracellular calcium signalling.Nature reviews. Molecular cell biology · 2025Review
- Cellular and molecular mechanisms of pathological tau phosphorylation in traumatic brain injury: implications for chronic traumatic encephalopathy.Molecular neurodegeneration · 2025Review
- Compound exposure of 2.8 GHz and 9.3 GHz microwave causes learning and memory impairment in rats.Heliyon · 2025Article
- Organelle abnormalities in Alzheimer's disease.Organelle (Tucson, Ariz.) · 2025Article
- Presenilins as hub proteins controlling the endocytic and autophagic pathways and small extracellular vesicle secretion.Journal of extracellular vesicles · 2025Article
- Lost in translation: Inconvenient truths on the utility of mouse models in Alzheimer's disease research.eLife · 2024Review
- Prevention and Treatment Strategies for Alzheimer's Disease: Focusing on Microglia and Astrocytes in Neuroinflammation.Journal of inflammation research · 2024Review
- NPC1-dependent alterations in KNature communications · 2023Article
- Role of Calcium Modulation in the Pathophysiology and Treatment of Alzheimer's Disease.International journal of molecular sciences · 2023Review
- "Dirty Dancing" of Calcium and Autophagy in Alzheimer's Disease.Life (Basel, Switzerland) · 2023Review
- Neuronal loss of NCLX-dependent mitochondrial calcium efflux mediates age-associated cognitive decline.iScience · 2023Article
- Regulation of Ryanodine Receptor-Dependent Neurotransmitter Release by AIP, Calstabins, and Presenilins.Advances in neurobiology · 2023Article
- Protein mishandling and impaired lysosomal proteolysis generated through calcium dysregulation in Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- 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
85 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Disruptions in intracellular Ca2+ signaling are proposed to underlie the pathophysiology of Alzheimer's disease (AD), and it has recently been shown that AD-linked mutations in the presenilin 1 gene (PS1) enhance inositol triphosphate (IP3)-mediated Ca2+ liberation in nonexcitable cells. However, little is known of these actions in neurons, which are the principal locus of AD pathology. We therefore sought to determine how PS1 mutations affect Ca2+ signals and their subsequent downstream effector functions in cortical neurons. Using whole-cell patch-clamp recording, flash photolysis, and two-photon imaging in brain slices from 4-5-week-old mice, we show that IP3-evoked Ca2+ responses are more than threefold greater in PS1(M146V) knock-in mice relative to age-matched nontransgenic controls. Electrical excitability is thereby reduced via enhanced Ca2+ activation of K+ conductances. Action potential-evoked Ca2+ signals were unchanged, indicating that PS1(M146V) mutations specifically disrupt intracellular Ca2+ liberation rather than reduce cytosolic Ca2+ buffering or clearance. Moreover, IP3 receptor levels are not different in cortical homogenates, further suggesting that the exaggerated cytosolic Ca2+ signals may result from increased store filling and not from increased flux through additional IP3-gated channels. Even in young animals, PS1 mutations have profound effects on neuronal Ca2+ and electrical signaling: cumulatively, these disruptions may contribute to the long-term pathophysiology of AD.
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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.