A5081340796- Neuroinflammation and Neurodegeneration Mechanisms
- Amyotrophic Lateral Sclerosis Research
- Alzheimer's disease research and treatments
- Nerve injury and regeneration
- Immune cells in cancer
- Neurogenetic and Muscular Disorders Research
- Viral gastroenteritis research and epidemiology
- Muscle Physiology and Disorders
- Histone Deacetylase Inhibitors Research
- Parkinson's Disease Mechanisms and Treatments
- S100 Proteins and Annexins
- Spinal Cord Injury Research
- Tryptophan and brain disorders
- Medicinal Plants and Neuroprotection
- Atherosclerosis and Cardiovascular Diseases
- Influenza Virus Research Studies
- Dementia and Cognitive Impairment Research
- Nuclear Receptors and Signaling
- Respiratory viral infections research
- Neurological Disease Mechanisms and Treatments
- Neurogenesis and neuroplasticity mechanisms
- Immune Response and Inflammation
- Spinal Dysraphism and Malformations
- Mesenchymal stem cell research
- Science, Technology, and Education in Latin America
VIB-KU Leuven Center for Brain & Disease Research
2020-2025
Vlaams Instituut voor Biotechnologie
2021-2024
Universitat Autònoma de Barcelona
2014-2021
Centro de Investigación Biomédica en Red
2014-2021
Biomedical Research Networking Center on Neurodegenerative Diseases
2014-2021
KU Leuven
2020
University of Cienfuegos
2019
The brain is a site of relative immune privilege. Although CD4 T cells have been reported in the central nervous system, their presence healthy remains controversial, and function largely unknown. We used combination imaging, single cell, surgical approaches to identify CD69+ cell population both mouse human brain, distinct from circulating cells. brain-resident was derived through situ differentiation activated circulatory shaped by self-antigen peripheral microbiome. Single-cell sequencing...
Macrophages and microglia play a key role in the maintenance of nervous system homeostasis. However, upon different challenges, they can adopt several phenotypes, which may lead to divergent effects on tissue repair. After spinal cord injury (SCI), macrophages show predominantly pro-inflammatory activation contribute damage. factors that hamper their conversion an anti-inflammatory state after SCI, or other protective are poorly understood. Here, we IL-4 protein levels undetectable contusion...
Abstract Microglia are central players in Alzheimer’s disease pathology but analyzing microglial states human brain samples is challenging due to genetic diversity, postmortem delay and admixture of pathologies. To circumvent these issues, here we generated 138,577 single-cell expression profiles stem cell-derived microglia xenotransplanted the App NL-G-F model amyloid wild-type controls. Xenografted adopt a disease-associated profile similar that seen mouse microglia, display more...
Abstract Inflammation is a common neuropathological feature in several neurological disorders, including amyotrophic lateral sclerosis (ALS). We have studied the contribution of CSF1R signalling to inflammation ALS, as pathway previously reported control expansion and activation microglial cells. found that cell proliferation spinal cord SOD1 G93A transgenic mice correlates with expression its ligand CSF1. Administration GW2580, selective inhibitor, reduced mice, indicating importance...
γ-Secretases mediate the regulated intramembrane proteolysis (RIP) of more than 150 integral membrane proteins. We developed an unbiased γ-secretase substrate identification (G-SECSI) method to study what extent these proteins are processed in parallel. demonstrate here parallel processing at least 85 human microglia steady-state cell culture conditions. Pharmacological inhibition caused substantial changes microglial transcriptomes, including expression genes related disease-associated...
While immune function is known to play a mechanistic role in Alzheimer's disease (AD), whether proteins peripheral circulation influence the rate of amyloid-β (Aβ) progression – central feature AD remains unknown. In Baltimore Longitudinal Study Aging, we quantified 942 immunological plasma and identified 32 (including CAT [catalase], CD36 [CD36 antigen], KRT19 [keratin 19]) associated with rates cortical Aβ accumulation measured positron emission tomography (PET). changes subset candidate...
Abstract Background Recent studies highlight the critical role of microglia in neurodegenerative disorders, and emphasize need for humanized models to accurately study microglial responses. Human-mouse xenotransplantation are a valuable platform functional testing therapeutic approaches, yet currently those only available academic research. This hampers their implementation development medication that targets human microglia. Methods We developed hCSF1 Bdes mouse line, which is suitable as...
Duchenne muscle dystrophy (DMD) is a genetic disorder characterized by progressive skeletal weakness. Dystrophin deficiency induces instability of the sarcolemma during contraction that leads to necrosis and replacement fibro-adipose tissue. Several therapies have been developed counteract fibrotic process. We report effects nintedanib, tyrosine kinase inhibitor, in mdx murine model DMD. Nintedanib reduced proliferation migration human fibroblasts vitro decreased expression genes such as...
Microglial activation and neuroinflammation are initial steps in the pathogenesis of Alzheimer’s disease (AD). However, studies mouse models human postmortem samples have yielded divergent results regarding microglia cell states relevant to AD. Here, we investigate 127,000 single expression profiles isolated freshly from a xenotransplantation model for early While adopt disease-associated (DAM) profile, they display much more pronounced HLA-cell state related antigen presentation response...
Abstract Spinal cord injury (SCI) leads to irreversible devastating neurological disabilities. Accumulated evidence in the literature indicates that inflammatory response occurs spinal following contributes importantly spread tissue damage healthy regions adjacent lesion site, and consequently, increase deficits. Therefore, targeting inflammation could lead development of new therapies prevent impairments after SCI. Inflammation is regulated, part, by expression pro‐inflammatory...
Amyotrophic lateral sclerosis (ALS) is a lethal motor neuron disease with no cure. Currently there are only two ALS drugs approved by the FDA, both limited therapeutic effect. In search for drug candidates ALS, we studied effect of known stem cell mobilizing agents (treatment) and antimetabolite 5-fluorouracil (5-FU) (anti-treatment) in SOD1G93A model ALS. Surprisingly, found that anti-cancer 5-FU increases lifespan, delays onset improves performance mice. Although were not able to...
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive muscle weakness, paralysis and death. There no effective treatment for ALS stem cell therapy has arisen as potential therapeutic approach. SOD1 mutant mice were used to study the neurotrophic effect of bone marrow cells grafted into quadriceps femoris muscle. Bone intramuscular transplants resulted in increased longevity with improved motor function decreased motoneuron degeneration spinal cord....
Abstract Using high resolution quantitative mass spectrometry, we have generated the most comprehensive human and mouse microglia proteomic datasets to date, consisting of over 11,000 proteins across all six groups. Microglia from different sources share a core protein signature 5600 proteins, yet fundamental differences are observed between species culture conditions, indicating limitations for disease modelling in or vitro cultures microglia. Mouse ex vivo show important at proteome level...
Abstract Background The simultaneous contribution of several etiopathogenic disturbances makes amyotrophic lateral sclerosis (ALS) a fatal and challenging disease. Here, we studied two different cell therapy protocols to protect both central peripheral nervous system in murine model ALS. Methods Since ALS begins with distal axonopathy, first assay, performed injection bone marrow cells into hindlimb muscles transgenic SOD1 G93A mice. In second study, combined intramuscular intraspinal cells....
Lysophosphatidic acid (LPA) is a pleiotropic extracellular lipid mediator with many physiological functions that signal through six known G protein-coupled receptors (LPA 1–6 ). In the central nervous system (CNS), LPA mediates wide range of effects including neural progenitor cell physiology, neuronal death, axonal retraction, and inflammation. Since inflammation hallmark most neurological conditions, we hypothesized could be involved in physiopathology amyotrophic lateral sclerosis (ALS)....
Abstract Background While immune function is known to play a mechanistic role in Alzheimer’s disease (AD), whether proteins peripheral circulation influence the rate of amyloid‐b (Aβ) progression remains unknown. Method Using Baltimore Longitudinal Study Aging (BLSA; n = 196; mean follow‐up: 5 years/4 scans), we identified immune‐related plasma ( candidate ) related rates change cortical Aβ levels, as measured by 11 C‐PiB PET. Along with identifying genetic variants that contributed protein...
Abstract Background Neuroinflammation is a pathological hallmark of Alzheimer’s disease (AD). Murine studies have revealed that mouse microglia can adopt several cell states in response to insults. However, single‐nuclei RNA sequencing found divergent results when recalling those human post‐mortem tissue. Method To overcome this limitation, we sequenced 127,000 single isolated from an AD xenotransplantation model. Result In plaques, including disease‐associated (DAM) and antigen‐presenting...