A5034468688- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Complement system in diseases
- Phagocytosis and Immune Regulation
- Cell Adhesion Molecules Research
- Barrier Structure and Function Studies
- S100 Proteins and Annexins
- Drug Transport and Resistance Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- Tryptophan and brain disorders
- Immune cells in cancer
- Gut microbiota and health
- Immune Cell Function and Interaction
- Neuroscience and Neuropharmacology Research
- Neurological Disease Mechanisms and Treatments
- Bioinformatics and Genomic Networks
- Computational Drug Discovery Methods
- Receptor Mechanisms and Signaling
- Glycosylation and Glycoproteins Research
- Blood groups and transfusion
- Cancer-related cognitive impairment studies
- Advanced Drug Delivery Systems
University of California, Irvine
2016-2025
University of California, San Francisco
2021-2023
Oslo University Hospital
2021
University of Oslo
2021
University of Copenhagen
2021
Rigshospitalet
2021
Norwegian University of Science and Technology
2021
Nordland Hospital
2021
Irvine University
2017
Irvine Valley College
2017
This study undertakes a systematic and comprehensive analysis of brain gene expression profiles immune/inflammation-related genes in aging Alzheimer's disease (AD). In well-powered microarray young (20 to 59 years), aged (60 99 AD (74 95 years) cases, responses were assessed the hippocampus, entorhinal cortex, superior frontal gyrus, post-central gyrus. Several novel concepts emerge. First, showed major changes over course cognitively normal aging, with extent response far greater than AD....
The decline of cognitive function has emerged as one the greatest health threats old age. Age-related is caused by an impacted neuronal circuitry, yet molecular mechanisms responsible are unknown. C1q, initiating protein classical complement cascade and powerful effector peripheral immune response, mediates synapse elimination in developing CNS. Here we show that C1q levels dramatically increase normal aging mouse human brain, much 300-fold. This was predominantly localized close proximity...
The complement cascade not only provides protection from infection but can also mediate destructive inflammation. Complement is involved in elimination of neuronal synapses which essential for proper development, be detrimental during aging and disease. C1q, required several these complement-mediated activities, present the neuropil, microglia, a subset interneurons brain.To identify source(s) C1q brain, C1qa gene was selectively inactivated microglia or Thy-1+ neurons both wild type mice...
A new procedure for isolating human C1q from serum or plasma is described. The method, that highly selective, rapid and involves minimal handling, yields fully active, immunoglobulin-free unaggregated C1q. Several different methods of radiolabeling are compared. These include two selective tyrosine residues, label lysine a method labels sialic acid residues. effect each the labeling procedures on hemolytic activity was assessed. Also appraised ability labeled molecules to bind antibody...
Abstract Mouse models of human diseases are invaluable tools for studying pathogenic mechanisms and testing interventions therapeutics. For disorders such as Alzheimer’s disease in which numerous being generated, a challenging first step is to identify the most appropriate model age effectively evaluate new therapeutic approaches. Here we conducted detailed phenotypic characterization 5xFAD on congenic C57BL/6 J strain background, across its lifespan – including seldomly analyzed 18-month...
With severe injury or disease, microglia become chronically activated and damage the local brain environment, likely contributing to cognitive decline. We previously discovered that are dependent on colony-stimulating factor 1 receptor (CSF1R) signaling for survival in healthy adult brain, we have exploited this dependence determine whether such contribute deleteriously functional recovery following a neuronal lesion. Here, induced hippocampal lesion mice 25 d via expression of diphtheria...
Abstract Deficiency in C1q, the recognition component of classical complement cascade and a pattern receptor involved apoptotic cell clearance, leads to lupus-like autoimmune diseases characterized by auto-antibodies self proteins aberrant innate immune activation likely due impaired clearance cells. In this study, we developed an autologous system using primary human lymphocytes monocyte-derived macrophages (HMDMs) characterize effect C1q on macrophage gene expression profiles during uptake...
ABSTRACT Alternative splicing is widely acknowledged to be a crucial regulator of gene expression and key contributor both normal developmental processes disease states. While cost-effective accurate for quantification, short-read RNA-seq lacks the ability resolve full-length transcript isoforms despite increasingly sophisticated computational methods. Long-read sequencing platforms such as Pacific Biosciences (PacBio) Oxford Nanopore (ONT) bypass reconstruction challenges short reads. Here...
Animal models of disease are valuable resources for investigating pathogenic mechanisms and potential therapeutic interventions. However, complex disorders such as Alzheimer's (AD), the generation availability innumerous distinct animal present unique challenges to AD researchers hinder success useful therapies. Here, we conducted an in-depth analysis 3xTg-AD mouse model across its lifespan better inform field various pathologies that appear at specific ages, comment on drift has occurred in...
beta-amyloid peptides that accumulate within the brain of individuals with Alzheimer's disease bind to C1q and activate classical C pathway via a specific interaction site collagen-like domain (C1q-CLF). Synthetic analogues peptides, beta 1-42 1-40, bound were strong activators as assessed by both total consumption C4 consumption. was significantly more effective than 1-40 in binding triggering activation, whereas 1-28 demonstrated little or no activation. This C-activating capacity seems be...
Glycoprotein adhesion receptors such as selectins contribute to tissue injury in stroke. Ischemic neurons strongly expressed C1q, which may target them for complement-mediated attack or C1qRp-mediated clearance. A hybrid molecule was used simultaneously inhibit both complement activation and selectin-mediated adhesion. The extracellular domain of soluble receptor–1 (sCR1) sialyl Lewis x glycosylated (sCR1sLe ) endothelial-platelet-leukocyte interactions. sCR1 sCR1sLe colocalized ischemic...
C1q, the recognition component of classical complement activation pathway, is a multifunctional protein known to be expressed in brain Alzheimer's disease (AD) patients. To experimentally address role C1q AD, mouse model lacking (APPQ-/-) was generated by crossing Tg2576 animals (APP) with C1q-deficient mice. The pathology APPQ-/- compared that APP mice and B6SJL controls at 3-16 months age immunohistochemistry Western blot analysis. At younger ages (3-6 months), when no plaque present,...
C1q, a subunit of the first component (C1) classical complement pathway, and pulmonary surfactant protein SP-A are structurally homologous molecules, each having an extended collagen-like domain contiguous with non-collagenous domain. It is region C1q that binds to mononuclear phagocytes mediates enhancement phagocytosis opsonized particles by these cells. Because enhances endocytosis phospholipids alveolar type II cells macrophages, we examined whether two molecules were functionally...
Abstract Alzheimer’s disease (AD) is an age-related dementia, characterized by amyloid plaques, neurofibrillary tangles, neuroinflammation, and neuronal loss in the brain. Components of complement system, known to produce a local inflammatory reaction, are associated with plaques tangles AD brain, thus role for complement-mediated inflammation acceleration or progression has been proposed. A activation product, C5a, recruit activate microglia astrocytes vitro G protein-coupled cell-surface...