A5010680026- Neuroinflammation and Neurodegeneration Mechanisms
- IL-33, ST2, and ILC Pathways
- Alzheimer's disease research and treatments
- Neurological Disease Mechanisms and Treatments
- Tryptophan and brain disorders
- Advanced Fluorescence Microscopy Techniques
- Optical Coherence Tomography Applications
- Eosinophilic Esophagitis
- Photoacoustic and Ultrasonic Imaging
- Asthma and respiratory diseases
- Regulation of Appetite and Obesity
- Biochemical Analysis and Sensing Techniques
- Immune cells in cancer
- Axon Guidance and Neuronal Signaling
- Neuroscience and Neuropharmacology Research
- Neurogenesis and neuroplasticity mechanisms
Hong Kong University of Science and Technology
2019-2023
University of Hong Kong
2019-2023
Hong Kong Science and Technology Parks Corporation
2021-2023
Alzheimer's disease (AD) is the most common form of dementia but has no effective treatment. A comprehensive investigation cell type-specific responses and cellular heterogeneity in AD required to provide precise molecular targets for therapeutic development. Accordingly, we perform single-nucleus transcriptome analysis 169,496 nuclei from prefrontal cortical samples patients normal control (NC) subjects. Differential shows that transcriptomic changes are associated with disruption...
Impairment of microglial clearance activity contributes to beta-amyloid (Aβ) pathology in Alzheimer's disease (AD). While the transcriptome profile microglia directs functions, how can be regulated alleviate AD is largely unknown. Here, we show that injection interleukin (IL)-33 an transgenic mouse model ameliorates Aβ by reprogramming epigenetic and transcriptomic profiles induce a subpopulation with enhanced phagocytic activity. These IL-33-responsive (IL-33RMs) express distinct signature...
Abstract In Alzheimer’s disease (AD), sensome receptor dysfunction impairs microglial danger-associated molecular pattern (DAMP) clearance and exacerbates pathology. Although extrinsic signals, including interleukin-33 (IL-33), can restore DAMP clearance, it remains largely unclear how the is regulated interacts with during phagocytic clearance. Here, we show that IL-33 induces VCAM1 in microglia, which promotes chemotaxis toward amyloid-beta (Aβ) plaque-associated ApoE, leads to Aβ We...
Changes in the levels of circulating proteins are associated with Alzheimer's disease (AD), whereas their pathogenic roles AD unclear. Here, we identified soluble ST2 (sST2), a decoy receptor interleukin-33-ST2 signaling, as new disease-causing factor AD. Increased sST2 level is more severe pathological changes female individuals Genome-wide association analysis and CRISPR-Cas9 genome editing rs1921622 , genetic variant an enhancer element IL1RL1, which downregulates gene protein sST2....
Alzheimer's disease (AD), the most common neurodegenerative disease, has limited treatment options. As such, extensive studies have been conducted to identify novel therapeutic approaches. We previously reported that rhynchophylline (Rhy), a small molecule EphA4 inhibitor, rescues impaired hippocampal synaptic plasticity and cognitive dysfunctions in APP/PS1 mice, an AD transgenic mouse model. To assess whether Rhy can be developed as alternative for AD, it is important examine its...
Alzheimer's disease (AD) is a devastating neurodegenerative disorder with no disease-modifying treatment. AD progression characterized by cognitive decline, neuroinflammation, and accumulation of amyloid-beta (Aβ) neurofibrillary tangles in the brain, leading to neuronal glial dysfunctions. Neuropeptides govern diverse pathophysiological processes represent key players pathogenesis, regulating synaptic plasticity, cell functions amyloid pathology. Activation pro-opiomelanocortin...
Alzheimer's disease is characterized by the deposition of extracellular amyloid-beta (Aβ) plaques. While microglial phagocytosis a major mechanism through which Aβ cleared, there no method for quantitatively assessing phagocytic capacity microglia in vivo. Here, we present flow cytometry-based investigating This enables direct comparison between different subpopulations as well isolation downstream applications. For complete details on use and execution this protocol, please refer to Lau et...
Imaging of the brain in its native state at high spatial resolution poses major challenges to visualization techniques. Two-photon microscopy integrated with thinned-skull or optical clearing skull technique provides a minimally invasive tool for vivo imaging cortex mice without activating immune response and inducing injury. However, contrast are severely compromised by heterogeneity skull, limiting depth superficial layer. In this work, an optimized configuration adaptive optics two-photon...
Adult hippocampal neurogenesis involves the lifelong generation of neurons. The process depends on homeostasis production neurons and maintenance adult neural stem cell (NSC) pool. Here, we report that α2-chimaerin, a Rho GTPase-activating protein, is essential for NSC in neurogenesis. Conditional deletion α2-chimaerin NSCs resulted premature differentiation into intermediate progenitor cells (IPCs), which ultimately depleted pool impaired neuron generation. Single-cell RNA sequencing...
Abstract Imaging of the brain in its native state at high resolution poses major challenges to visualization techniques. Two-photon microscopy integrated with thinned-skull or optical clearing skull technique provides a minimally invasive tool for vivo imaging cortex mice without activating immune response and inducing injury. However, contrast are severely compromised by heterogeneity skull, limiting depth superficial layer. Here, we develop adaptive optics two-photon high-resolution...
Abstract Background Genetic factors are increasingly being recognized as important contributors to the pathogenesis of Alzheimer’s disease (AD). While expression most AD risk genes is enriched in microglia, which leads microglial dysfunction and amyloid‐beta (Aβ) accumulation, emerging studies suggest that changes brain micro‐environment—typically levels soluble factors—also modulate functions disease‐related pathological changes. Therefore, understanding genetic regulation pathogenic roles...