A5078066242- Alzheimer's disease research and treatments
- Wnt/β-catenin signaling in development and cancer
- Mitochondrial Function and Pathology
- Genetic Neurodegenerative Diseases
- Nuclear Receptors and Signaling
- Cellular transport and secretion
- Endoplasmic Reticulum Stress and Disease
- RNA Research and Splicing
- Genetics and Neurodevelopmental Disorders
- Amyotrophic Lateral Sclerosis Research
- Microtubule and mitosis dynamics
- 14-3-3 protein interactions
- Cancer-related gene regulation
- Receptor Mechanisms and Signaling
- Insect and Arachnid Ecology and Behavior
- Neuroscience and Neuropharmacology Research
- Cancer-related Molecular Pathways
- Bioinformatics and Genomic Networks
- Genomics and Chromatin Dynamics
- Signaling Pathways in Disease
- Epigenetics and DNA Methylation
- Protein Kinase Regulation and GTPase Signaling
- Axon Guidance and Neuronal Signaling
- Circular RNAs in diseases
- Neurogenesis and neuroplasticity mechanisms
Chinese University of Hong Kong
2016-2025
Creative Commons
2023
École Polytechnique Fédérale de Lausanne
2023
Christie's
2020
Tuen Mun Hospital
2018
Institute of Cytochemistry and Molecular Pharmacology
2018
Shenzhen Institutes of Advanced Technology
2018
Chinese Academy of Sciences
2018
King's College London
2000-2014
Institute of Molecular and Cell Biology
2011-2012
Abstract Mitochondria and the endoplasmic reticulum (ER) form tight structural associations these facilitate a number of cellular functions. However, mechanisms by which regions ER become tethered to mitochondria are not properly known. Understanding is just important for comprehending fundamental physiological processes but also understanding pathogenic in some disease states. In particular, disruption ER–mitochondria linked neurodegenerative diseases. Here we show that ER-resident protein...
A proline to serine substitution at position 56 in the gene encoding vesicle-associated membrane protein-associated protein B (VAPB) causes some dominantly inherited familial forms of motor neuron disease including amyotrophic lateral sclerosis (ALS) type-8. VAPB is an integral endoplasmic reticulum (ER) whose amino-terminus projects into cytosol. Overexpression ALS mutant VAPBP56S disrupts ER structure but mechanisms by which it induces are not properly understood. Here we show that...
Amyotrophic lateral sclerosis (ALS) is a late-onset neurological disorder characterized by death of motoneurons. Mutations in Cu/Zn superoxide dismutase-1 (SOD1) cause familial ALS but the mechanisms whereby they induce disease are not fully understood. Here, we use time-lapse microscopy to monitor for first time effect mutant SOD1 on fast axonal transport (FAT) bona fide cargoes living neurons. We analyzed FAT mitochondria that known target damage and also membrane-bound organelles (MBOs)...
Abstract Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the predominant impairment of neurons in hippocampus and formation amyloid plaques, hyperphosphorylated tau protein, neurofibrillary tangles brain. The overexpression amyloid-β precursor protein (APP) an AD brain results binding APP intracellular domain (AICD) to Fe65 via C-terminal Fe65-PTB2 interaction, which then triggers secretion consequent pathogenesis AD. Apparently, targeting interaction between can...
Using an elementary physical model for protein folding, of self-avoiding short copolymer chains on two-dimensional square lattices, we address two questions regarding the evolution and origins globular proteins. (i) How will native structures stabilities be affected by single-and double-site mutations? (ii) What is probability that a randomly chosen sequence amino acids compact under folding conditions? For large number different sequences, search conformational space exhaustively to find...
The cell nucleus is a major site for polyglutamine (polyQ) toxicity, but the underlying mechanisms involved have yet been fully elucidated. Here, we report that mutant RNAs carry an expanded CAG repeat (expanded RNAs) induce apoptosis by activating nucleolar stress pathway in both polyQ patients and transgenic animal disease models. We showed interacted directly with nucleolin (NCL), protein regulates rRNA transcription. Such RNA-protein interaction deprived NCL of binding to upstream...
Haploinsufficiency of GRN, the gene encoding progranulin (PGRN), causes frontotemporal lobar degeneration (FTLD), second most common cause early-onset dementia. Receptor-mediated lysosomal targeting has been shown to regulate brain PGRN levels, and complete deficiency is a direct neuronal ceroid lipofuscinosis (NCL), storage disease. Here we show that cysteine protease cathepsin L (Cat L) can mediate proteolytic cleavage intracellular into poly-granulin granulin fragments. Further, Cat...
Objective: RAC1 aberrations in head and neck squamous cell carcinoma (HNSCC) remain clinically inactionable today. Methods: Here, we investigated the clinical significance potential druggability of genomic HNSCC. Results: Notably, HPV(−)HNSCC patients bearing unique HNSCC-prevalent RAC1-A159V hotspot mutation, P29S G-box domain mutations, copy number increases all displayed dismal overall survival (TCGA-HNSCC). demonstrated that five HNSCC patient-relevant tested (A159V K116N, G15S, N39S)...
The amyloidogenic pathway leading to the production and deposition of Abeta peptides, major constituents Alzheimer disease senile plaques, is linked neuronal metal homeostasis. amyloid precursor protein binds copper zinc in its extracellular domain, peptides also bind copper, zinc, iron. first step generation cleavage by aspartic protease BACE1. Here we show that BACE1 interacts with CCS (the chaperone for superoxide dismutase-1 (SOD1)) through domain I proteins co-immunoprecipitate from rat...
<h3>Background</h3> Spinocerebellar ataxias (SCAs) are a group of clinically and genetically diverse autosomal-dominant disorders characterised by neurological deficits in the cerebellum. At present, there is no cure for SCAs. Of different distinct subtypes SCAs identified to date, causative genes only fraction them currently known. In this study, we investigated cause an SCA phenotype family that exhibits cerebellar ataxia pontocerebellar atrophy along with global reduction brain volume....
Threonine 668 (thr ) within the carboxy‐terminus of Alzheimer's disease amyloid precursor protein (APP) is a known in vivo phosphorylation site. Phosphorylation APPthr believed to regulate APP function and metabolism. Thr precedes proline, which suggests that it targeted for by proline‐directed kinase(s). We have investigated ability four major neuronally active kinases, cyclin dependent kinase‐5, glycogen synthase kinase‐3β, p42 mitogen‐activated kinase stress‐activated kinase‐1b,...
Abstract: Human glycogen synthase kinase‐3 (GSK‐3) is a multisubstrate, proline‐directed kinase that phosphorylates tau, β‐amyloid and neurofilaments. In this study, the expression levels of two GSK‐3 isoforms, α β, RNA proteins in different human tissues were examined. Northern analysis demonstrated GSK‐3α encoded by 2.6‐kb mRNA GSK‐3β 8.3‐ 2.8‐kb mRNAs. The species variably expressed tissues. quantitative polymerase chain reaction both prominently testis, thymus, prostate ovary but low...
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, has developed multiple strategies to adapt human host. The five type VII secretion systems, ESX-1–5, direct export many virulence-promoting protein effectors across complex mycobacterial cell wall. One class ESX substrates is PE–PPE family proteins, which unique mycobacteria and essential for infection, antigenic variation, host–pathogen interactions. genome Mtb encodes 168 proteins. Many them are thought be secreted...
Amyloid precursor protein (APP), best known for its association with Alzheimer disease, has recently been implicated in breast cancer progression. However, the precise mechanism involved remains unclear. Here, we investigated role of APP proteolytic cleavage functions.The presence products was examined cell lines. The functional roles were studied vitro and tumor xenograft model using siRNA. effects full length α-secretase cleaved ectodomain fragment, soluble APPα (sAPPα) further their...
Abstract The neuronal cyclin‐dependent kinase p35/cdk5 comprises a catalytic subunit (cdk5) and an activator (p35). To identify novel substrates, we utilized the yeast two‐hybrid system to screen for human p35 binding partners. From one such screen, identified β‐catenin as interacting protein. Confirmation that binds was obtained by using glutathione S‐transferase (GST)–β‐catenin fusion proteins interacted with both endogenous transfected p35, showing present in immunoprecipitates. also...
Increased production and deposition of the 40-42-amino acid β-amyloid peptide (Aβ) is believed to be central pathogenesis Alzheimer's disease. Aβ derived from amyloid precursor protein (APP), but mechanisms that regulate APP processing produce are not fully understood. X11α (also known as munc-18-interacting protein-1 (Mint1)) a neuronal adaptor binds modulates in transfected non-neuronal cells. To investigate vivo effect on brain, we created transgenic mice overexpress crossed these with...
Alzheimer's disease (AD) is a common form of dementia which characterized by the deposition amyloids in affected neurons and cholinergic neurotransmission deficit brain. The current therapeutic intervention for AD primarily based on inhibition brain acetylcholinesterase (AChE) to restore acetylcholine level. Cryptotanshinone (CT) diterpene extracted from root Salvia miltiorrhiza, herb that commonly prescribed Chinese medicine treat cardiovascular disease. In present study, we demonstrated CT...
The ribonucleoprotein (RNP) complex is the essential transcription-replication machinery of influenza virus. It composed trimeric polymerase (PA, PB1 and PB2), nucleoprotein (NP) RNA. Elucidating molecular mechanisms RNP assembly central to our understanding control viral transcription replication dependence these processes on host cell. In this report, we show, by reconstitution assays co-immunoprecipitation, that interaction between NP crucial for function RNP. functional association...
A number of viral gene products are capable inducing apoptosis by interfering with various cellular signalling cascades. We previously reported the pro-apoptotic property SARS-CoV (severe acute respiratory syndrome coronavirus) M (membrane)-protein and a down-regulation phosphorylation level cell-survival protein PKB (protein kinase B)/Akt in cells expressing M-protein. also showed that overexpression PDK1 (3-phosphoinositide-dependent 1), immediate upstream PKB/Akt, suppressed M-induced...
Expanded CAG RNA has recently been reported to contribute neurotoxicity in polyglutamine (polyQ) degeneration. In this study, we showed that carrying an expanded repeat progressively accumulated the cell nucleus of transgenic Drosophila displayed Our gene knockdown and mutant analyses demonstrated reduction U2AF50 function, a involved nuclear export, intensified accumulation resulted concomitant exacerbation RNA-mediated toxicity vivo. We found human ortholog, U2AF65, interacted directly...