ArticleJournal of cellular and molecular medicine2009
Presenilin-2 dampens intracellular Ca2+ stores by increasing Ca2+ leakage and reducing Ca2+ uptake.
Article in Journal of cellular and molecular medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 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
- Astrocyte CaBiomolecules · 2026Review
- STIM Proteins: The Gas and Brake of Calcium Entry in Neurons.Neuroscience bulletin · 2025Review
- Endoplasmic reticulum stress-related deficits in calcium clearance promote neuronal dysfunction that is prevented by SERCA2 gene augmentation.Cell reports. Medicine · 2024Article
- Altered expression of Presenilin2 impacts endolysosomal homeostasis and synapse function in Alzheimer's disease-relevant brain circuits.Nature communications · 2024Article
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- Review
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- Patients with Darier Disease Exhibit Cognitive Impairment while Patients with Hailey-Hailey Disease Do Not: An Experimental, Matched Case-control Study.Acta dermato-venereologica · 2021Article
- Chronic but not acute pharmacological activation of SERCA induces behavioral and neurochemical effects in male and female mice.Behavioural brain research · 2021Article
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- Alterations of the Endoplasmic Reticulum (ER) Calcium Signaling Molecular Components in Alzheimer's Disease.Cells · 2020Review
- Review
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- ORAI2 Down-Regulation Potentiates SOCE and Decreases Aβ42 Accumulation in Human Neuroglioma Cells.International journal of molecular sciences · 2020Article
- Intracellular Calcium Dysregulation by the Alzheimer's Disease-Linked Protein Presenilin 2.International journal of molecular sciences · 2020Review
- Presenilin-Deficient Neurons and Astrocytes Display Normal Mitochondrial Phenotypes.Frontiers in neuroscience · 2020Article
- PSEN2 (presenilin 2) mutants linked to familial Alzheimer disease impair autophagy by altering CaAutophagy · 2019Article
- The SERCA2: A Gatekeeper of Neuronal Calcium Homeostasis in the Brain.Cellular and molecular neurobiology · 2018Review
- Endoplasmic reticulum-resident selenoproteins as regulators of calcium signaling and homeostasis.Cell calcium · 2018Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have previously shown that familial Alzheimer's disease mutants of presenilin-2 (PS2) and, to a lesser extent, of presenilin-1 (PS1) lower the Ca(2+) concentration of intracellular stores. We here examined the mechanism by which wild-type and mutant PS2 affect store Ca(2+) handling. By using HeLa, SH-SY5Y and MEFs as model cells, and recombinant aequorins as Ca(2+) probes, we show evidence that transient expression of either wild-type or mutant PS2 increases the passive Ca(2+) leakage: both ryanodine- and IP(3)-receptors contribute to Ca(2+) exit out of the ER, whereas the ribosome translocon complex is not involved. In SH-SY5Y cells and MEFs, wild-type and mutant PS2 potently reduce the uptake of Ca(2+) inside the stores, an effect that can be counteracted by over-expression of SERCA-2B. On this line, in wild-type MEFs, lowering the endogenous level of PS2 by RNA interference, increases the Ca(2+)-loading capability of intracellular stores. Furthermore, we show that in PS double knockout MEFs, reduction of Ca(2+) stores is mimicked by the expression of PS2-D366A, a loss-of-function mutant, uncleaved because also devoid of presenilinase activity but not by co-expression of the two catalytic active fragments of PS2. In summary, both physiological and increased levels of wild-type and mutant PS2 reduce the Ca(2+) uptake by intracellular stores. To exert this newly described function, PS2 needs to be in its full-length form, even if it can subsequently be cleaved.
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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.