A5012017576- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Immune cells in cancer
- Inflammation biomarkers and pathways
- Extracellular vesicles in disease
- GDF15 and Related Biomarkers
- Phagocytosis and Immune Regulation
- Amyotrophic Lateral Sclerosis Research
- Vagus Nerve Stimulation Research
- Histone Deacetylase Inhibitors Research
- Neurological Disease Mechanisms and Treatments
- Nuclear Receptors and Signaling
- Neurogenesis and neuroplasticity mechanisms
- Receptor Mechanisms and Signaling
- Medicinal Plants and Bioactive Compounds
- Complement system in diseases
- Long-Term Effects of COVID-19
University College London
2020-2024
UK Dementia Research Institute
2020-2024
Alzheimer's disease (AD) is characterized by synaptic loss, which can result from dysfunctional microglial phagocytosis and complement activation. However, what signals drive aberrant microglia-mediated engulfment of synapses in AD unclear. Here we report that secreted phosphoprotein 1 (SPP1/osteopontin) upregulated predominantly perivascular macrophages and, to a lesser extent, fibroblasts. Perivascular SPP1 required for microglia engulf upregulate phagocytic markers including C1qa, Grn...
Abstract Dipeptide repeat proteins are a major pathogenic feature of C9orf72 amyotrophic lateral sclerosis (C9ALS)/frontotemporal dementia (FTD) pathology, but their physiological impact has yet to be fully determined. Here we generated dipeptide knock-in mouse models characterized by expression 400 codon-optimized polyGR or polyPR repeats, and heterozygous reduction. (GR)400 (PR)400 mice recapitulate key features C9ALS/FTD, including cortical neuronal hyperexcitability, age-dependent spinal...
Abstract The abnormal assembly of tau protein in neurons is a pathological hallmark multiple neurodegenerative diseases, including Alzheimer’s disease (AD). Assembled associates with extracellular vesicles (EVs) the central nervous system individuals AD, which linked to its clearance and prion-like propagation. However, identities assembled species EVs, as well how they associate, are not known. Here, we combined quantitative mass spectrometry, cryo-electron tomography single-particle...
SUMMARY The abnormal assembly of tau protein in neurons is the pathological hallmark multiple neurodegenerative diseases, including Alzheimer’s disease (AD). In addition, assembled associates with extracellular vesicles (EVs) central nervous system patients AD, which linked to its clearance and prion-like propagation between neurons. However, identities species EVs, as well how they associate, are not known. Here, we combined quantitative mass spectrometry, cryo-electron tomography...
Summary Region-specific synapse loss is an early pathological hallmark in Alzheimer’s disease (AD). Emerging data mice and humans highlight microglia, the brain-resident macrophages, as cellular mediators of loss; however, upstream modulators microglia-synapse engulfment remain elusive. Here, we report a distinct subset astrocytes, which are glial cells essential for maintaining homeostasis, appearing region-specific manner with age amyloidosis at onset loss. These astrocytes distinguished...
Summary Microglia are phagocytes of the brain parenchyma, where they interact with neurons to engulf synapses in a context-dependent manner. Genetic studies Alzheimer’s disease (AD) highlight dysfunctional phagocytic signaling myeloid cells as disease-associated pathway. In AD models, there is region-specific reactivation microglia-synapse phagocytosis involving complement; however, what drives engulfment remains unknown. Here, we show that SPP1 (Osteopontin), glycoprotein associated...
It is becoming increasingly clear that the dominant, century-old neurocentric view of neurodegeneration insufficient to explain why certain neurons degenerate, in particular with aging. Genetic studies patient populations as well mechanistic and functional animal models altogether implicate nonneuronal cells, especially glia, play more than bystander roles neurodegeneration. Throughout life span, neuronal function homeostasis are modulated by functions which become even critical This review...
C1q, the initiating protein of classical complement cascade, mediates synapse loss in development and disease. In various mouse models neurologic diseases, including Alzheimer's disease, which is secreted by microglia, brain's resident macrophages, found deposited on synapses vulnerable brain regions. However, what underlies C1q deposition adult unclear. Using vivo chemogenetics, we demonstrate that neuronal hyperactivity acts as a trigger for region-specific required activity-dependent...