A5025513711- Neuroinflammation and Neurodegeneration Mechanisms
- Multiple Sclerosis Research Studies
- Inflammation biomarkers and pathways
- Neurological Disease Mechanisms and Treatments
- Dietary Effects on Health
- Cytokine Signaling Pathways and Interactions
- Immunotherapy and Immune Responses
- Gut microbiota and health
- T-cell and B-cell Immunology
- Alzheimer's disease research and treatments
- Cell Adhesion Molecules Research
- Immune cells in cancer
- Diet and metabolism studies
- Systemic Lupus Erythematosus Research
- Immune Cell Function and Interaction
- RNA Research and Splicing
- Circular RNAs in diseases
- Circadian rhythm and melatonin
- Peripheral Neuropathies and Disorders
- Amyotrophic Lateral Sclerosis Research
- Cancer-related molecular mechanisms research
- MicroRNA in disease regulation
- Tryptophan and brain disorders
- Adipokines, Inflammation, and Metabolic Diseases
- RNA regulation and disease
Washington University in St. Louis
2016-2025
The University of Sydney
2019-2024
Hope Center for Neurological Disorders
2013-2023
University of Milan
1999-2022
University Medical Center Groningen
2022
Nini Hospital
2022
Istituto di Istruzione Secondaria Superiore "V. Lilla" Francavilla Fontana - Oria
2022
Kaiser Permanente
2022
Oregon Health & Science University
2022
Los Angeles Medical Center
2022
Abstract The triggering receptor expressed on myeloid cells 2 (TREM-2) delivers intracellular signals through the adaptor DAP12 to regulate cell function both within and outside immune system. role of TREM-2 in immunity has been obscured by failure detect expression protein vivo. In this study, we show that is macrophages infiltrating tissues from circulation alternative activation with IL-4 can induce TREM-2. abrogated macrophage maturation LPS IFN-γ. Using TREM-2−/− mice, find functions...
Dietary interventions have not been effective in the treatment of multiple sclerosis (MS). Here, we show that periodic 3-day cycles a fasting mimicking diet (FMD) are ameliorating demyelination and symptoms murine experimental autoimmune encephalomyelitis (EAE) model. The FMD reduced clinical severity all mice completely reversed 20% animals. These improvements were associated with increased corticosterone levels regulatory T (Treg) cell numbers pro-inflammatory cytokines, TH1 TH17 cells,...
Recent genome-wide association studies linked variants in TREM2 to a strong increase the odds of developing Alzheimer’s disease. The mechanism by which influences susceptibility disease is currently unknown. expressed microglia and thought regulate phagocytic inflammatory microglial responses brain pathology. Given that single allele variant TREM2, likely resulting loss function, conferred an increased risk disease, we tested whether one functional trem2 would affect Aβ plaque deposition or...
Abstract Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system (CNS) triggered by autoimmune mechanisms. Microglia are critical for clearance myelin debris in areas demyelination, a key step to allow remyelination. TREM2 expressed microglia promotes microglial survival, proliferation, phagocytic activity. Herein we demonstrate that was highly on myelin-laden phagocytes active demyelinating lesions CNS subjects with MS. In gene...
TREM2 is a transmembrane receptor that predominantly expressed by microglia in the central nervous system. Rare variants gene increase risk for late-onset Alzheimer's disease (AD). Soluble (sTREM2) resulting from shedding of ectodomain can be detected cerebrospinal fluid (CSF) and surrogate measure TREM2-mediated function. CSF sTREM2 has been previously reported to at different clinical stages AD, however, alterations relation Amyloid β-peptide (Aβ) deposition or additional pathological...
<h3>Background</h3> B cells are implicated in the pathogenesis of multiple sclerosis. A beneficial effect B-cell depletion using rituximab has been shown, but complete mechanism action for this drug is unclear. <h3>Objective</h3> To determine relationship between T and changes cerebrospinal fluid (CSF) chemokine levels with rituximab, a monoclonal antibody that targets CD20. <h3>Design</h3> Phase 2 trial as an add-on therapy. <h3>Setting</h3> The John L. Trotter Multiple Sclerosis Center,...
Higher CSF sTREM2 concentrations are associated with slower rates of cognitive decline in subjects Alzheimer’s disease.
Common variants in the microglia-specific MS4A gene cluster modify risk for late-onset Alzheimer’s disease and modulate extracellular soluble TREM2.
Multiple sclerosis (MS) has a complex genetic, immune and metabolic pathophysiology. Recent studies implicated the gut microbiome in MS pathogenesis. However, interactions between host system, metabolism diet have not been studied over time this disorder.We performed six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting patients 25 age, sex, race matched healthy control individuals. Gut composition function were characterized using 16S metagenomic...
Triggering receptor expressed on myeloid cells 2 (TREM-2) is a membrane-bound by microglia and macrophages. Engagement of TREM-2 these has been reported to reduce inflammatory responses and, in microglial cells, promote phagocytosis. function critical within the CNS, as its genetic deficiency humans causes neurodegeneration with myelin axonal loss. Blockade worsened mouse model for multiple sclerosis. In present study, soluble form protein identified immunoprecipitation ELISA. Soluble...
Abstract Triggering receptor expressed on myeloid cells (TREM‐2) is a membrane associated with DAP12 that primarily in cells, including dendritic and microglia, promotes fusion of osteoclast precursors into multinucleated cells. A rare autosomal recessive condition, Nasu‐Hakola disease (NHD) loss‐of‐function mutations TREM‐2. The brain pathology observed NHD patients suggests disruption the TREM‐2/DAP12 pathway leads to neurodegeneration demyelination axonal loss. In this study, we have...
Abstract Lymphocyte recruitment into the brain is a critical event in pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis. We developed novel intravital microscopy model to directly analyze through skull interactions between lymphocytes endothelium cerebral venules mice. No adhesive were observed nonactivated microcirculation. When activated by pretreating mice with TNF-α or LPS, proteolipid protein 139–151 autoreactive T rolled arrested; notably, only few...
Abstract Calorie restriction (CR) prevents many age-associated diseases and prolongs the lifespan. CR induces multiple metabolic physiologic modifications, including anti-inflammatory, antioxidant, neuroprotective effects that may be beneficial in sclerosis (MS). The present studies sought to determine whether or increased calorie intake alters course of experimental autoimmune encephalomyelitis (EAE), leading animal model for MS. SJL C57BL/6 mice were subjected 40% beginning at 5 weeks age....
B cells and the humoral immune system have been implicated in pathogenesis of multiple sclerosis (MS). This study sought to evaluate efficacy, safety, tolerability add-on therapy with rituximab, a monoclonal antibody that depletes circulating cells, subjects relapsing MS breakthrough disease defined by clinical MRI activity (Class III evidence).Thirty relapse within past 18 months despite use an injectable disease-modifying agent, at least 1 gadolinium-enhancing (GdE) lesion on any 3...
Multiple sclerosis (MS) is an inflammatory disease of the CNS that characterized by BBB dysfunction and has a much higher incidence in females. Compared with other strains mice, EAE SJL mouse strain models multiple features MS, including enhanced sensitivity female mice to disease; however, molecular mechanisms underlie sex- strain-dependent differences susceptibility have not been described. We identified sphingosine-1-phosphate receptor 2 (S1PR2) as strain-specific, disease-modifying...
CXCL13, a B-cell chemokine, has been proposed as biomarker in variety of conditions, some which can mimic multiple sclerosis and have very high levels. In this case-control study, cerebrospinal fluid (CSF) CXCL13 was elevated sclerosis, neuromyelitis optica other inflammatory neurological controls compared with noninflammatory controls. Levels did not differentiate disease groups. For all subjects taken together, CSF correlated WBC, oligoclonal band numbers, protein, EDSS, neurofilament...