A5009537822- Amyotrophic Lateral Sclerosis Research
- Alzheimer's disease research and treatments
- Parkinson's Disease Mechanisms and Treatments
- Nuclear Receptors and Signaling
- Neurogenetic and Muscular Disorders Research
- Endoplasmic Reticulum Stress and Disease
- Cerebrospinal fluid and hydrocephalus
- Neurogenesis and neuroplasticity mechanisms
- Cellular transport and secretion
- High Altitude and Hypoxia
- Mitochondrial Function and Pathology
- Cholinesterase and Neurodegenerative Diseases
- Wnt/β-catenin signaling in development and cancer
- Migraine and Headache Studies
- Glioma Diagnosis and Treatment
- biodegradable polymer synthesis and properties
- Lysosomal Storage Disorders Research
- RNA regulation and disease
- Zebrafish Biomedical Research Applications
- Protease and Inhibitor Mechanisms
- Electrochemical Analysis and Applications
- Protein Tyrosine Phosphatases
- ATP Synthase and ATPases Research
- Genetic Neurodegenerative Diseases
- Physiological and biochemical adaptations
University of Chinese Academy of Sciences
2016-2021
Shanghai Advanced Research Institute
2016-2021
Shanghai Institute of Materia Medica
2016-2021
Chinese Academy of Sciences
2016-2020
The University of Melbourne
2011-2017
Mental Health Research Institute
2011
Gyeongsang National University Hospital
2008
Mutations in the metallo-protein Cu/Zn-superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS) humans and an expression level-dependent phenotype transgenic rodents. We show that oral treatment with therapeutic agent diacetyl-bis(4-methylthiosemicarbazonato)copper<sup>II</sup> [Cu<sup>II</sup>(atsm)] increased concentration of mutant SOD1 (SOD1G37R) ALS model mice, but paradoxically improved locomotor function survival mice. To determine why mice levels had phenotype, we...
Amyotrophic lateral sclerosis (ALS) is a progressive paralyzing disease characterized by tissue oxidative damage and motor neuron degeneration. This study investigated the in vivo effect of diacetylbis(N(4)-methylthiosemicarbazonato) copper(II) (CuII(atsm)), which an orally bioavailable, blood-brain barrier-permeable complex. In vitro compound inhibits action peroxynitrite on Cu,Zn-superoxide dismutase (SOD1) subsequent nitration cellular proteins. Oral treatment transgenic SOD1G93A mice...
Abstract Ubiquitous expression of mutant Cu/Zn-superoxide dismutase (SOD1) selectively affects motor neurons in the central nervous system (CNS), causing adult-onset degenerative disease amyotrophic lateral sclerosis (ALS). The CNS-specific impact ubiquitous SOD1 is recapitulated transgenic mouse models disease. Here we present outcomes for metallo-complex Cu II (atsm) tested therapeutic efficacy mice expressing G93A on a mixed genetic background. Oral administration delayed onset...
Our objective was to assess the copperII complex of diacetylbis(4-methylthiosemicarbazone) [CuII(atsm)] for its preclinical potential as a novel therapeutic ALS. Experimental paradigms used were designed CuII(atsm) efficacy relative treatment with riluzole, function dose administered, and when administered post symptom onset. Mice expressing human Cu/Zn superoxide dismutase harbouring disease-causing G37R mutation (SOD1-G37R) effects determined by assessing mouse survival locomotor (rotarod...
The cerebrospinal fluid (CSF) is a valuable body for analysis in neuroscience research. It one of the fluids closest contact with central nervous system and thus, can be used to analyze diseased state brain or spinal cord without directly accessing these tissues. However, mice it difficult obtain from cisterna magna due its closeness blood vessels, which often contaminate samples. area CSF collection also dissect only small samples are obtained (maximum 5-7 µL less). This protocol describes...
Pathological changes in the Alzheimer's disease (AD) brain include amyoid-β (Aβ) plaques, and neurofibrillary tangles, as well neuronal death synaptic loss. Matrix metalloproteinases MMP-2 MMP-9 are known to degrade Aβ, their expressio
Disrupted metal homeostasis is a consistent feature of neurodegenerative disease in humans and recapitulated mouse models Alzheimer's disease, Parkinson's amyotrophic lateral sclerosis (ALS) neuronal ceriod lipofuscinosis. While the definitive pathogenesis remains to be fully elucidated, disease-like symptoms are all driven by presence or over-expression putative pathogenic protein, indicating an vivo relationship between expression these proteins, disrupted failure. Recently it was...
All cases of Huntington's disease (HD) are caused by mutant huntingtin protein (mhtt), yet the molecular mechanisms that link mhtt to symptoms not fully elucidated. Given glycogen synthase kinase-3 (GSK3) is implicated in several neurodegenerative diseases as a mediator neuronal decline and widely touted therapeutic target, we investigated GSK3 cells expressing mhtt, brains R6/1 HD mice post-mortem human brain samples. Consistency data across two models samples indicate decreased signalling...
The cerebrospinal fluid (CSF) is a valuable body for analysis in neuroscience research. It one of the fluids closest contact with central nervous system and thus, can be used to analyze diseased state brain or spinal cord without directly accessing these tissues. However, mice it difficult obtain from cisterna magna due its closeness blood vessels, which often contaminate samples. area CSF collection also dissect only small samples are obtained (maximum 5-7 µL less). This protocol describes...
Phosphoinositides and their metabolizing enzymes are involved in Aβ42 metabolism Alzheimer's disease pathogenesis. In yeast mammals, Eighty-five requiring 3 (EFR3), whose Drosophila homolog is Rolling Blackout (RBO), forms a plasma membrane-localized protein complex with phosphatidylinositol-4-kinase Type IIIα (PI4KIIIα) scaffold to tightly control the level of plasmalemmal phosphatidylinositol-4-phosphate (PI4P). Here, we report that RBO binds PI4KIIIα, an Aβ42-expressing model, separate...
Alzheimer's disease (AD) is characterized by deficits in learning and memory abilities, as well pathological changes of amyloid-β (Aβ) plaque neurofibrillary tangle formation the brain. Insulin has been identified a modulator neuronal pathways involved memory, also implicated Aβ tau metabolism. Disrupted insulin signaling are evident AD patients it understood that type 2 diabetes can increase risk developing AD, suggesting possible link between metabolic disorders neurodegeneration. SH2B1...
Neuronal amyloid-β (Aβ) accumulation plays an important role in the pathogenesis of Alzheimer's disease (AD). The conformation and toxicity Aβ are regulated by lipids on plasma membrane. Previously, we found downregulation Rolling Blackout (RBO) or phosphatidylinositol-4-kinase type IIIα (PI4KIIIα) reduces neuronal associated neural deficits a Drosophila model expressing Aβ42. In mammals, homologs RBO PI4KIIIα were reported to form membrane-localized complex with scaffold protein TTC7...
Besides degradation, lysosomes can also carry molecules for secretion out of the cell, such as ATP and cytokines, during unconventional secretion. Phosphatidylinositols their metabolizing enzymes play important roles in sorting trafficking lysosomal materials through trans-Golgi network. The present study reveals a new function phosphatidylinositol kinase-III alpha ‘kiss-and-run’ fusion at plasma membrane to release from microglia.
Hyccin/FAM126A mutations are linked to hypomyelination and congenital cataract disease (HCC), but whether how deficiency causes remains undetermined. This study shows expression was necessary for the of other components PI4KIIIα complex in Drosophila. Knockdown glia reduced enrichment glial cells, disrupted axonal sheaths visual ability system, these defects could be fully rescued by overexpressing either human FAM126A or FAM126B, partially a plasma membrane-targeting recombinant mouse...