ArticleExperimental neurology2013
Presenilins regulate the cellular activity of ryanodine receptors differentially through isotype-specific N-terminal cysteines.
Article in Experimental neurology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
- 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
- Regulation of Ryanodine Receptor-Dependent Neurotransmitter Release by AIP, Calstabins, and Presenilins.Advances in neurobiology · 2023Article
- Review
- Calcium Signaling Regulated by Cellular Membrane Systems and Calcium Homeostasis Perturbed in Alzheimer's Disease.Frontiers in cell and developmental biology · 2022Review
- CaCells · 2020Review
- Loss of presenilin 2 age-dependently alters susceptibility to acute seizures and kindling acquisition.Neurobiology of disease · 2020Article
- Dantrolene : From Malignant Hyperthermia to Alzheimer's Disease.CNS & neurological disorders drug targets · 2019Review
- Presenilins as Drug Targets for Alzheimer's Disease-Recent Insights from Cell Biology and Electrophysiology as Novel Opportunities in Drug Development.International journal of molecular sciences · 2018Review
- Neuronal Ryanodine Receptors in Development and Aging.Molecular neurobiology · 2018Review
- Kv channel-interacting proteins as neuronal and non-neuronal calcium sensors.Channels (Austin, Tex.) · 2018Review
- Ryanodine Receptors in Autophagy: Implications for Neurodegenerative Diseases?Frontiers in cellular neuroscience · 2018Review
- KChIP2 regulates the cardiac Ca2+ transient and myocyte contractility by targeting ryanodine receptor activity.PloS one · 2017Article
- Loss of Spatial Memory, Learning, and Motor Function During Normal Aging Is Accompanied by Changes in Brain Presenilin 1 and 2 Expression Levels.Molecular neurobiology · 2015Article
- Differential subcellular Ca2+ signaling in a highly specialized subpopulation of astrocytes.Experimental neurology · 2015Article
- Insert sequence length determines transfection efficiency and gene expression levels in bicistronic mammalian expression vectors.International journal of biochemistry and molecular biology · 2013Article
- Regulation of ryanodine receptor-mediated calcium signaling by presenilins.Receptors & clinical investigationArticle
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Presenilins (PS), endoplasmic reticulum (ER) transmembrane proteins, form the catalytic core of γ-secretase, an amyloid precursor protein processing enzyme. Mutations in PS lead to Alzheimer's disease (AD) by altering γ-secretase activity to generate pathologic amyloid beta and amyloid plaques in the brain. Here, we identified a novel mechanism where binding of a soluble, cytosolic N-terminal domain fragment (NTF) of PS to intracellular Ca(2+) release channels, ryanodine receptors (RyR), controls Ca(2+) release from the ER. While PS1NTF decreased total RyR-mediated Ca(2+) release, PS2NTF had no effect at physiological Ca(2+) concentrations. This differential function and isotype-specificity is due to four cysteines absent in PS1NTF, present, however, in PS2NTF. Site-directed mutagenesis targeting these cysteines converted PS1NTF to PS2NTF function and vice versa, indicating differential RyR binding. This novel mechanism of intracellular Ca(2+) regulation through the PS-RyR interaction represents a novel target for AD drug development and the treatment of other neurodegenerative disorders that critically depend on RyR and PS signaling.
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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.