ArticleScience signaling2016
Familial Alzheimer's disease-associated presenilin 1 mutants promote γ-secretase cleavage of STIM1 to impair store-operated Ca2+ entry.
Article in Science signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 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
- STIM-Orai signaling in neurons: integrating calcium dynamics and synaptic plasticity.Cell communication and signaling : CCS · 2026Review
- Genetic ablation of neuronal mitochondrial calcium uptake impedes Alzheimer's disease progression.The EMBO journal · 2026Article
- Role of dysregulated calcium homeostasis in astrocytes in neurodegenerative disorders.Nature reviews. Neuroscience · 2026Review
- The diverse forms and roles of the neuronal endoplasmic reticulum.Nature reviews. Neuroscience · 2026Review
- The CaCell reports. Medicine · 2026Article
- Abnormal calcium activity and CREB phosphorylation are associated with motor memory impairment in presenilin-1 mutant knock-in mice.Cell calcium · 2025Article
- The complex web of membrane contact sites in brain aging and neurodegeneration.Cellular and molecular life sciences : CMLS · 2025Review
- Low-frequency rTMS Plays a Neuroprotective role in Pilocarpine-induced Status Epilepticus Rat Models Through the AMPAR GluA1-STIM-CaMolecular neurobiology · 2025Article
- STIM Proteins: The Gas and Brake of Calcium Entry in Neurons.Neuroscience bulletin · 2025Review
- Store-Operated Calcium Channels in the Nervous System.Annual review of physiology · 2025Review
- Organelle abnormalities in Alzheimer's disease.Organelle (Tucson, Ariz.) · 2025Article
- Article
- Ginsenosides Decrease β-Amyloid Production via Potentiating Capacitative Calcium Entry.Biomolecules & therapeutics · 2024Article
- Intranasal CEPO-FC prevents attention deficits in streptozotocin-induced rat model of Alzheimer's disease: Focus on synaptic plasticity-related factors.EXCLI journal · 2024Article
- Familial Alzheimer's disease-associated PSEN1 mutations affect neurodevelopment through increased Notch signaling.Stem cell reports · 2023Article
- Rescue of astrocyte activity by the calcium sensor STIM1 restores long-term synaptic plasticity in female mice modelling Alzheimer's disease.Nature communications · 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
- Article
- Internalized Amyloid-β (1-42) Peptide Inhibits the Store-Operated Calcium Entry in HT-22 Cells.International journal of molecular sciences · 2022Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Some forms of familial Alzheimer's disease (FAD) are caused by mutations in presenilins (PSs), catalytic components of a γ-secretase complex that cleaves target proteins, including amyloid precursor protein (APP). Calcium (Ca(2+)) dysregulation in cells with these FAD-causing PS mutants has been attributed to attenuated store-operated Ca(2+) entry [SOCE; also called capacitative Ca(2+) entry (CCE)]. CCE occurs when STIM1 detects decreases in Ca(2+) in the endoplasmic reticulum (ER) and activates ORAI channels to replenish Ca(2+) stores in the ER. We showed that CCE was attenuated by PS1-associated γ-secretase activity. Endogenous PS1 and STIM1 interacted in human neuroblastoma SH-SY5Y cells, patient fibroblasts, and mouse primary cortical neurons. Forms of PS1 with FAD-associated mutations enhanced γ-secretase cleavage of the STIM1 transmembrane domain at a sequence that was similar to the γ-secretase cleavage sequence of APP. Cultured hippocampal neurons expressing mutant PS1 had attenuated CCE that was associated with destabilized dendritic spines, which were rescued by either γ-secretase inhibition or overexpression of STIM1. Our results indicate that γ-secretase activity may physiologically regulate CCE by targeting STIM1 and that restoring STIM1 may be a therapeutic approach in AD.
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Registered trials
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