A5027935456- Neuroinflammation and Neurodegeneration Mechanisms
- Spinal Cord Injury Research
- Neuroscience and Neuropharmacology Research
- RNA regulation and disease
- Traumatic Brain Injury and Neurovascular Disturbances
- PI3K/AKT/mTOR signaling in cancer
- Immune cells in cancer
- Treatment of Major Depression
- Nitric Oxide and Endothelin Effects
- Tryptophan and brain disorders
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Ion channel regulation and function
- Medical Imaging Techniques and Applications
- Organometallic Complex Synthesis and Catalysis
- Cancer-related molecular mechanisms research
- Asymmetric Hydrogenation and Catalysis
- S100 Proteins and Annexins
- Metal complexes synthesis and properties
- Chronic Lymphocytic Leukemia Research
- Nerve injury and regeneration
- Protein Tyrosine Phosphatases
- Receptor Mechanisms and Signaling
- Alzheimer's disease research and treatments
- Traumatic Brain Injury Research
- Immune Response and Inflammation
McGill University
2022-2024
Cancer Institute (WIA)
2024
Uniformed Services University of the Health Sciences
2015-2023
Henry M. Jackson Foundation
2023
McGill University Health Centre
2020
Universidade de Santiago de Compostela
2020
Excessive iron contributes to oxidative stress after central nervous system injury. NADPH oxidase (NOX) enzymes are upregulated in microglia pro-inflammatory activation and contribute stress. The relationship between iron, microglia, NOX, is currently unclear. We evaluated the effects of on lipopolysaccharide (LPS)-activated its secondary effect within neuronal co-cultures. Further, NOX2 four specific inhibitors were tested evaluate with reactive oxygen species (ROS)-producing enzymes. An...
Spinal cord injury (SCI) results in the activation of NADPH oxidase (NOX) enzyme, inducing production reactive oxygen species (ROS). We hypothesized that NOX2 isoform plays an integral role post-SCI inflammation and functional deficits. Moderate spinal contusion was performed adult male mice, flow cytometry, western blot, immunohistochemistry were used to assess activity expression, inflammation, M1/M2 microglia/macrophage polarization from 1 28 days after injury. The NOX2-specific...
Microglia are the macrophages of central nervous system (CNS), which function to monitor and maintain homeostasis. Microglial activation occurs after CNS injury, infection or disease. Prolonged microglial is detrimental as they produce nitric oxide (NO), reactive oxygen species (ROS) pro-inflammatory cytokines, resulting in neuronal cell dysfunction death. implicated neurological deficits following traumatic brain injury (TBI) Alzheimer's Intranasal insulin administration a promising...
Abstract INTRODUCTION Impaired brain protein synthesis, synaptic plasticity, and memory are major hallmarks of Alzheimer's disease (AD). The ketamine metabolite ( 2R,6R )‐hydroxynorketamine (HNK) has been shown to modulate but its effects on in AD models remain elusive. METHODS We investigated the HNK hippocampal long‐term potentiation (LTP), mouse models. RESULTS activated extracellular signal‐regulated kinase 1/2 (ERK1/2), mechanistic target rapamycin (mTOR), p70S6 1 (S6K1)/ribosomal S6...
Repeated mild traumatic brain injury (rmTBI) results in worsened outcomes, compared with a single injury, but the mechanism of this phenomenon is unclear. We have previously shown that TBI rat lateral fluid percussion model globally depressed glucose uptake, peak depression at 24 h resolves by 16 days post-injury. The current study investigated outcomes repeat conducted various times during period uptake. Adult male rats were therefore subjected to rmTBI latency h, 5 days, or 15 between...
Non-invasive measurements of brain metabolism using 18F-fluorodeoxyglucose (FDG) with positron emission tomography (PET) may provide important information about injury severity following traumatic (TBI). There is growing interest in the potential combining functional PET imaging anatomical and magnetic resonance (MRI). This study aimed to investigate effectiveness clinically available FDG-PET T2 diffusion MR imaging, a particular focus on inflammation influence glial alterations after...
Reactive oxygen species (ROS) are a contributing factor to impaired function and pathology after spinal cord injury (SCI). The NADPH oxidase (NOX) enzyme is key source of ROS; there several NOX family members, including NOX2 NOX4, that may play role in ROS production SCI. Previously, we showed temporary inhibition by intrathecal administration gp91ds-tat immediately improved recovery mouse SCI model. However, chronic inflammation was not affected this single acute treatment, other members...
Abstract In Alzheimer’s Disease (AD), activation of the mechanistic target rapamycin (mTOR) pathway is essential for microglia neuroprotective roles, but it unclear which mTOR effectors promote these functions. The complex 1 (mTORC1) inactivates translation suppressors eukaryotic Initiation Factor 4E (eIF4E)-Binding Proteins (4E-BP) to mRNA translation. We show that 4E-BP1 inactivation impaired in under AD-relevant conditions. Depleting 4E-BPs increases mitochondrial metabolism, suppresses...
The mRNA 5'cap-binding eukaryotic translation initiation factor 4E (eIF4E) plays a critical role in the control of health and disease. One mechanism regulation eIF4E activity is via phosphorylation by MNK kinases, which promotes subset mRNAs encoding pro-tumorigenic proteins. Work on phosphatases has been paltry. Here, we show that PPM1G phosphatase dephosphorylates eIF4E. We describe eIF4E-binding motif similar to 4E-binding proteins (4E-BPs). demonstrate inhibits cell proliferation...
Abstract Background Activation of the mTOR pathway is pivotal for microglia to induce and sustain neuroprotective functions (Ulland et al., 2017; Wang 2022). complex 1 (mTORC1) inhibits translation repressors, eukaryotic Initiation Factor 4E (eIF4E)‐Binding Proteins (4E‐BPs), via phosphorylation, which causes their release from eIF4E promote mRNA (Hay Sonenberg, 2004). mTORC1 promotes mitochondrial biogenesis inhibition 4E‐BPs, by preferentially stimulating mitochondria‐related mRNAs (Gandin...
Genetic perturbances in translational regulation result defects cerebellar motor learning; however, little is known about the role of mechanisms plasticity. We show that genetic removal 4E-BP, a suppressor and target mammalian rapamycin complex 1, results striking change synaptic find long-term depression (LTD) at parallel fiber-Purkinje cell synapses converted to potentiation 4E-BP knockout mice. Biochemical pharmacological experiments suggest increased phosphatase activity largely accounts...
Abstract The mRNA 5’cap-binding eukaryotic translation initiation factor 4E (eIF4E) plays a major role in control of health and disease. One mechanism regulation eIF4E activity is via phosphorylation by MNK kinases, which promotes the subset mRNAs encoding pro-tumorigenic pro-inflammatory proteins. Work on phosphatases has been paltry. Here, we show that PPM1G phosphatase dephosphorylates eIF4E. We describe binding motif shares an site with eIF4G 4E-binding proteins (4E-BPs)....
Abstract Impaired synaptic plasticity and progressive memory deficits are major hallmarks of Alzheimer’s disease (AD). Hippocampal mRNA translation, required for consolidation, is defective in AD. Here, we show that systemic treatment with ( 2R,6R )- hydroxynorketamine (HNK), an active metabolite the antidepressant ketamine, prevented hippocampal long-term potentiation (LTP) induced by AD-linked amyloid-β oligomers (AβOs) mice. HNK activated extracellular signal-regulated kinase 1/2...
Abstract Background Rare loss‐of‐function variants in TREM2 (Triggering Receptor Expressed Myeloid cells 2) are associated with an increased risk of AD. There ongoing efforts to therapeutically boost microglial neuroprotective functions by targeting TREM2. However, the intracellular mechanisms underlying these AD not fully understood. signaling maintains metabolic fitness through activation mechanistic target rapamycin (mTOR) allowing microglia sustain their metabolism during amyloidosis...
The synthesis of palladium cyclometallated compounds with thiosemicarbazone ligands is described,as well as their reactivity bidentate phosphine ligands. the carried out by a condensation reaction between ketone and thiosemicarbazide. Subsequently, metallation proceeds, resulting product reacted bis(diphenylphosphino)methane (dppm) using appropriate conditions to obtain compound in monodentate coordination mode.