ArticlePloS one2010
Presenilin 2 is the predominant γ-secretase in microglia and modulates cytokine release.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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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
37 citing papers in PubMed, 64 citations in OpenAlex.
- Distinct and shared effects of individual γ-secretase inhibitors on human keratinocytes.JID innovations : skin science from molecules to population health · 2026Article
- Loss of presenilin 2 function age-dependently increases susceptibility to kainate-induced acute seizures and blunts hippocampal kainate-type glutamate receptor expression.Experimental neurology · 2026Article
- In Silico Phosphoproteomic Analysis Reveals Divergent Regulation of Presenilin 1 and Presenilin 2.Neuromolecular medicine · 2026Article
- Integrated phenotypic and proteomic screening identifies top-tier Alzheimer's disease therapeutic targets.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- The connection between autophagy and Alzheimer's disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Integrated phenotypic and proteomic screening identifies top-tier Alzheimer's disease therapeutic targets.bioRxiv : the preprint server for biology · 2025Article
- Loss of presenilin 2 function age-dependently increases susceptibility to kainate-induced acute seizures and blunts hippocampal kainate-type glutamate receptor expression.bioRxiv : the preprint server for biology · 2025Article
- Endogenous γ-Secretase Is Linked to Phagocytic Activity in Microglial Cells.Sensors (Basel, Switzerland) · 2025Article
- Altered expression of Presenilin2 impacts endolysosomal homeostasis and synapse function in Alzheimer's disease-relevant brain circuits.Nature communications · 2024Article
- Chronic evoked seizures in young pre-symptomatic APP/PS1 mice induce serotonin changes and accelerate onset of Alzheimer's disease-related neuropathology.Progress in neurobiology · 2024Article
- Interictal spikes in Alzheimer's disease: Preclinical evidence for dominance of the dentate gyrus and cholinergic control by the medial septum.Neurobiology of disease · 2023Article
- Apoptin NLS2 homodimerization strategy for improved antibacterial activity and bio-stability.Amino acids · 2023Article
- Aberrant splicing of PSEN2, but not PSEN1, in individuals with sporadic Alzheimer's disease.Brain : a journal of neurology · 2023Article
- The Future of Precision Medicine in the Cure of Alzheimer's Disease.Biomedicines · 2023Review
- Loss of normal Alzheimer's disease-associated Presenilin 2 function alters antiseizure medicine potency and tolerability in the 6-Hz focal seizure model.Frontiers in neurology · 2023Article
- Alzheimer's Disease and Epilepsy: A Perspective on the Opportunities for Overlapping Therapeutic Innovation.Neurochemical research · 2021Review
- Review
- Loss of presenilin 2 age-dependently alters susceptibility to acute seizures and kindling acquisition.Neurobiology of disease · 2020Article
- Article
- Early-Onset Familial Alzheimer Disease Variant PSEN2 N141I Heterozygosity is Associated with Altered Microglia Phenotype.Journal of Alzheimer's disease : JAD · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Presenilin 1 (PS1) and Presenilin 2 (PS2) are the enzymatic component of the γ-secretase complex that cleaves amyloid precursor protein (APP) to release amyloid beta (Aβ) peptide. PS deficiency in mice results in neuroinflammation and neurodegeneration in the absence of accumulated Aβ. We hypothesize that PS influences neuroinflammation through its γ-secretase action in CNS innate immune cells. We exposed primary murine microglia to a pharmacological γ-secretase inhibitor which resulted in exaggerated release of TNFα and IL-6 in response to lipopolysaccharide. To determine if this response was mediated by PS1, PS2 or both we used shRNA to knockdown each PS in a murine microglia cell line. Knockdown of PS1 did not lead to decreased γ-secretase activity while PS2 knockdown caused markedly decreased γ-secretase activity. Augmented proinflammatory cytokine release was observed after knockdown of PS2 but not PS1. Proinflammatory stimuli increased microglial PS2 gene transcription and protein in vitro. This is the first demonstration that PS2 regulates CNS innate immunity. Taken together, our findings suggest that PS2 is the predominant γ-secretase in microglia and modulates release of proinflammatory cytokines. We propose PS2 may participate in a negative feedback loop regulating inflammatory behavior in microglia.
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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.