A5045077009- Neuroinflammation and Neurodegeneration Mechanisms
- Immune cells in cancer
- Alzheimer's disease research and treatments
- Inflammation biomarkers and pathways
- Tryptophan and brain disorders
- Endoplasmic Reticulum Stress and Disease
- Neurological Disease Mechanisms and Treatments
- GDF15 and Related Biomarkers
- Protein Kinase Regulation and GTPase Signaling
- Nuclear Receptors and Signaling
- Protein Tyrosine Phosphatases
- S100 Proteins and Annexins
- Autophagy in Disease and Therapy
- Psoriasis: Treatment and Pathogenesis
- Prion Diseases and Protein Misfolding
- Parasites and Host Interactions
- 14-3-3 protein interactions
- thermodynamics and calorimetric analyses
- Reproductive Physiology in Livestock
Humboldt-Universität zu Berlin
2020-2025
Charité - Universitätsmedizin Berlin
2012-2025
Freie Universität Berlin
2020-2025
University of Oxford
2020-2021
Southampton General Hospital
2017-2021
Alzheimer’s Research UK
2020-2021
University of Southampton
2017-2021
Discovery Institute
2020
Neuroinflammation and microglial activation are significant processes in Alzheimer's disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes with disease, experimental data demonstrated proliferation as a component of the neuropathology. In this study, we tested efficacy selective CSF1R inhibitor JNJ-40346527 (JNJ-527) P301S mouse tauopathy model. We first anti-proliferative effects JNJ-527 on microglia ME7 prion model, its impact inflammatory...
The sustained proliferation of microglia is a key hallmark Alzheimer's disease (AD), accelerating its progression. Here, we aim to understand the long-term impact early and prolonged microglial observed in AD, hypothesizing that extensive repeated cycling would engender distinct transcriptional phenotypic trajectory. We show seen an AD-like model promotes replicative senescence, characterized by increased βgal activity, senescence-associated signature, telomere shortening, correlating with...
Abstract Background TREM2 is a microglial cell surface receptor, with risk mutations linked to Alzheimer’s disease (AD), including R47H. signalling via SYK aids phagocytosis, chemotaxis, survival, and changes activation state. In AD mouse models, knockout (KO) of impairs clustering around amyloid prevents activation. The R47H mutation proposed reduce ligand binding. We investigated phenotypes the mutant KO in model human microglia, compared their transcriptional signatures, determine...
Abstract Neuroinflammation including interleukin (IL)-12/IL-23-signaling is central to Alzheimer’s disease (AD) pathology. Inhibition of p40, a subunit IL-12/IL-23, attenuates pathology in AD-like mice; however, its signaling mechanism and expression pattern remained elusive. Here we show that IL-12 receptors are predominantly expressed neurons oligodendrocytes APPPS1 mice patients with AD, whereas IL-23 receptor transcripts barely detectable. Consistently, deletion the neuroectodermal cells...
Article30 January 2020Open Access Source DataTransparent process Interleukin-12/23 deficiency differentially affects pathology in male and female Alzheimer's disease-like mice Pascale Eede orcid.org/0000-0002-0272-8607 Department of Neuropathology, corporate member Freie Universität Berlin, Humboldt-Universität zu Berlin Institute Health, Charité – Universitätsmedizin Germany Search for more papers by this author Juliane Obst Eileen Benke Genevieve Yvon-Durocher Bernhard C Richard Niclas...
Abstract Human genetic studies have linked rare coding variants in microglial genes, such as TREM2 , and more recently PLCG2 to Alzheimer’s disease (AD) pathology. The P522R variant has been shown confer protection for AD result a subtle increase enzymatic activity. PLCγ2 is key component of intracellular signal transduction networks induces Ca 2+ signals downstream many myeloid cell surface receptors, including TREM2. To explore the relationship between role regulating immune function, we...
The proliferation and activation of microglia, the resident macrophages in brain, is a hallmark many neurodegenerative diseases such as Alzheimer's disease (AD) prion disease. Colony stimulating factor 1 receptor (CSF1R) critically involved regulating microglial proliferation, CSF1R blocking strategies have been recently used to modulate microglia diseases. However, broadly expressed by cell types impact its inhibition on innate immune system still unclear. can be activated two independent...
Innate immune activation is a major driver of neurodegenerative disease and regulatory pathways could be potential targets for therapeutic intervention. Recently, Programmed cell death-1 (PD-1) checkpoint inhibition has been proposed to mount an IFN-γ-dependent systemic response, leading the recruitment peripheral myeloid cells brain neuropathological functional improvements in mice with Alzheimer's disease-like β-amyloid pathology. Here we investigate impact PD-1 deficiency on murine prion...
Abstract The proliferation and activation of microglia, the resident macrophages in brain, is a hallmark many neurodegenerative diseases such as Alzheimer’s disease (AD) prion disease. Colony stimulating factor 1 receptor (CSF1R) critically involved regulating microglial proliferation, CSF1R blocking strategies have been recently used to modulate microglia diseases. However, broadly expressed by cellular types impact its inhibition on innate immune system still unclear. can be activated two...
Abstract Background Genome wide association studies (GWAS) and systems biology approaches have identified several Alzheimer’s disease (AD) risk associated genes expressed in microglia. SHIP1, an inositol phosphatase, has been as a regulator of TREM2 signalling, inhibiting the cascade by opposing SYK PI3K phosphorylation. A SHIP1 variant (rs39349669) confers AD increasing expression, thereby signalling reducing beneficial microglial phenotypes including phagocytosis. We hypothesise that...
ABSTRACT The sustained proliferation of microglia is a key hallmark Alzheimer’s disease (AD), accelerating its progression. Here, we sought to understand the long-term impact early and prolonged microglial observed in AD, hypothesising that extensive repeated cycling would engender distinct transcriptional phenotypic trajectory. We found seen an AD-like model promotes replicative senescence, characterised by increased βgal activity, senescence-associated signature telomere shortening,...
Alzheimer's disease (AD) pathology displays an inflammatory component characterized by the presence of pro-inflammatory cytokines, particularly in response to β-amyloid. Previously, we observed increased production common interleukin (IL)-12 and IL-23 subunit p40 microglia transgenic APPPS1 mice, which serve as a model AD. Genetic ablation or its receptors resulted drastic decrease cerebral amyloid plaque load. The reduction burden was accompanied reduced activation microglia. Furthermore,...
Abstract BACKGROUND: TREM2 is a microglial cell surface receptor, with risk mutations linked to Alzheimer’s disease (AD), including R47H. Binding of ligands triggers Syk-dependent signalling through the DAP12 co-receptor, leading phagocytosis, survival, and changes activation state. In biochemical assays, R47H impairs binding phosphatidylserine, lipid “eat-me” signal exposed by apoptotic neurons. The effect upon phagocytosis neurons human microglia has not yet been reported. METHODS: We...