A5052899443- Alzheimer's disease research and treatments
- 14-3-3 protein interactions
- Neuroinflammation and Neurodegeneration Mechanisms
- Ubiquitin and proteasome pathways
- Drug Transport and Resistance Mechanisms
- Ion channel regulation and function
- Inflammation biomarkers and pathways
- Cancer, Lipids, and Metabolism
- Nuclear Receptors and Signaling
- Cholesterol and Lipid Metabolism
- Neuroscience and Neuropharmacology Research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Genetics and Neurodevelopmental Disorders
- Glycosylation and Glycoproteins Research
- Trace Elements in Health
- Endoplasmic Reticulum Stress and Disease
- Calcium signaling and nucleotide metabolism
- Glutathione Transferases and Polymorphisms
- Medicinal Plants and Neuroprotection
Occupational Cancer Research Centre
2015-2025
University of Toronto
2012-2025
University Health Network
2020-2021
RIKEN Center for Brain Science
2011
The University of Tokyo
2011
TREM2 is a pattern recognition receptor, expressed on microglia and myeloid cells, detecting lipids Aβ inducing an innate immune response. Missense mutations (e.g., R47H) of increase risk Alzheimer's disease (AD). The soluble ectodomain wild-type (sTREM2) has been shown to protect against AD in vivo, but the underlying mechanisms are unclear. We show that oligomers bind cellular TREM2, shedding sTREM2 domain. Wild-type bound (measured by single-molecule imaging, dot blots, Bio-Layer...
Amyloid beta oligomers (Aβos) are toxic to synapses and key the progression of Alzheimer's disease (AD) amyloid pathology, representing a target for therapeutic strategies. small ubiquitin modifier 2 (SUMO2) transgenics were analyzed by electrophysiology behavioral testing. A recombinant analogue SUMO2, SBT02, was generated assessed brain penetration ability mitigate pathology. Elevated SUMO2 expression prevents cognitive synaptic impairment in mouse model AD Systemic administration SBT02...
Sarco/endoplasmic reticulum (SR/ER) Ca2+-ATPase (SERCA) is an intracellular Ca2+ pump localized on the SR/ER membrane. The role of SERCA in refilling stores pivotal for maintaining homeostasis, and disturbed activity causes many disease phenotypes, including heart failure, diabetes, cancer, Alzheimer disease. Although has been described using a simple enzyme equation, dynamics living cells still unknown. To monitor cells, we constructed enhanced CFP (ECFP)- FlAsH-tagged SERCA2a, designated...
Abstract Rare coding variants of the microglial triggering receptor expressed on myeloid cells 2 (TREM2) confer an increased risk for Alzheimer's disease (AD) characterized by progressive accumulation aggregated forms amyloid β peptides (Aβ). Aβ are generated proteolytic processing precursor protein (APP). Heterogeneity in cleavages and additional post‐translational modifications result production several distinct that could differ their aggregation behavior toxic properties. Here, we sought...
ATP-binding cassette transporter A7 (ABCA7) is a member of the ABC family associated with phagocytosis. ABCA7 highly homologous to ABCA1, which act as critical gatekeeper regulating cellular cholesterol efflux extracellular apolipoprotein acceptors. Transcriptional regulation negatively regulated by cell cholesterol, mediated sterol regulatory element binding protein 2, in opposite direction that ABCA1. Genetic, biochemical and pharmacological evidences indicate alternations homeostasis...
Small ubiquitin-like modifiers (SUMO) are covalently conjugated to target proteins and modulate a growing number of cellular pathways. SUMOs have been strong links tumorgenesis metastasis due regulation nuclear events. More recently, increasing evidence has demonstrated their role in neuronal pathways such as synaptic plasticity memory well several neurodegenerative diseases.
Abstract Missense mutations (e.g. R47H) of the microglial receptor TREM2 increase risk Alzheimer’s disease (AD), and soluble ectodomain wild-type (sTREM2) appears to protect in vivo, but underlying mechanisms are unclear. We show that Aβ oligomers bind TREM2, inducing shedding sTREM2. Wild-type sTREM2 inhibits oligomerization, fibrillization neurotoxicity, disaggregates preformed protofibrils. In contrast, R47H AD-risk variant is less able disaggregate oligomeric Aβ, rather promotes...