A5047988796- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- RNA Research and Splicing
- Phytochemicals and Antioxidant Activities
- Amyotrophic Lateral Sclerosis Research
- Ubiquitin and proteasome pathways
- Cellular transport and secretion
- Epigenetics and DNA Methylation
- Autophagy in Disease and Therapy
- Chromatography in Natural Products
- DNA Repair Mechanisms
- Neuroscience and Neuropharmacology Research
- Natural product bioactivities and synthesis
- Neurogenetic and Muscular Disorders Research
- Microbial Natural Products and Biosynthesis
- Endoplasmic Reticulum Stress and Disease
- Wnt/β-catenin signaling in development and cancer
- Cell death mechanisms and regulation
- Lipid metabolism and biosynthesis
- Enzyme-mediated dye degradation
- Marine Sponges and Natural Products
- Plant biochemistry and biosynthesis
- Bioactive Compounds and Antitumor Agents
- RNA modifications and cancer
- Hedgehog Signaling Pathway Studies
Chinese University of Hong Kong
2014-2024
John Radcliffe Hospital
2023
University of Oxford
2023
Institute of Cytochemistry and Molecular Pharmacology
2018
Chinese Academy of Sciences
2013
<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....
Lignin-carbohydrate complex (LCC) is the biological macromolecule that has been demonstrated to exert multiple functions, including antioxidant, anti-inflammation and anti-tumorigenesis, which support its broad application in bioengineering field. However, it remains elusive involvements of LCC human neurological disorders, especially those with overproduction reactive oxygen species (ROS), such as spinocerebellar ataxias (SCAs). In this study, we found a previously undetermined anti-protein...
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...
Significance Small CAG (sCAG) RNAs are neurotoxic, but their role in polyglutamine degeneration remains to be fully elucidated. We observed that cellular expression of sCAGs is sufficient induce neuronal DNA damage and discovered the transcript level NUDT16 was reduced HD models. The protein has previously been linked pathway. At structural level, form double-stranded CAG–CUG heteroduplex RNA with which led its gene silencing. showed bisamidinium-based compound DB213 specifically interacts...
Polyglutamine (polyQ) diseases are a class of progressive neurodegenerative disorders characterized by the expression both expanded CAG RNA and misfolded polyQ protein. We previously reported that direct interaction between nucleolar protein nucleolin (NCL) impedes preribosomal ( pre-rRNA ) transcription, eventually triggers stress-induced apoptosis in diseases. Here, we report 21-amino acid peptide, named “beta-structured inhibitor for diseases” (BIND), effectively suppresses toxicity...
Abstract Polyglutamine (polyQ) diseases describe a group of progressive neurodegenerative disorders caused by the CAG triplet repeat expansion in coding region disease genes. To date, nine such diseases, including spinocerebellar ataxia type 3 ( SCA 3), have been reported. The formation SDS ‐insoluble protein aggregates neurons causes cellular dysfunctions, as impairment ubiquitin‐proteasome system, and contributes to polyQ pathologies. Recently, E3 ubiquitin ligases, which govern substrate...
Context: Epidioxy sterols and with special side chains, such as hydroperoxyl sterols, usually obtained from marine natural products, are attractive for bioactivities.Objective: To isolate screen bioactive China Sea invertebrates.Materials methods: Two (1 2) the sponge Xestospongia testudinaria Lamarck (Petrosiidae), three epidioxy (3–5) sea urchin Glyptocidaris crenularis A. Agassiz (Glyptocidaridae), Mycale sp. (Mycalidae) gorgonian Dichotella gemmacea Milne Edwards Haime (Ellisellidae) an...
The fuzzy planar cell polarity protein (Fuz) is an effector component of the (PCP) signaling. Together with other core and proteins, PCP pathway controls polarized movements. Fuz was also reported as a negative regulator survival. In this study, we performed pan-cancer survey to demonstrate role in multiple types cancer. head-neck squamous carcinoma lung adenocarcinoma tumor samples, reduction
One drug, two diseases is a rare and economical therapeutic strategy that highly desirable in the pharmaceutical industry. We previously reported 21-amino acid peptide named beta-structured inhibitor for neurodegenerative (BIND) can effectively inhibit expanded CAG trinucleotide toxicity polyglutamine (polyQ) diseases. Here we report BIND also inhibits GGGGCC repeat-mediated neurodegeneration vitro vivo. When fused with cell-penetrating derived from transactivator of transcription (TAT)...
Yin Yang 1 (YY1) is a multi-functional transcription factor that regulates gene expression in range of cell types, including neurons. It controls neuronal differentiation, as well specification and migration during the development mammalian nervous system. Besides, YY1 also mediates genes are required for survival. An impairment transcriptional function causes death. This review summarizes recent research findings unveil dysfunction multiple neurodegenerative disorders. The disease proteins...
The octomeric exocyst complex governs the final step of exocytosis in both plants and animals. Its roles, however, extend beyond include organelle biogenesis, ciliogenesis, cell migration, growth. Exo70 is a conserved component whose function Drosophila unclear. In this study, we characterized two mutant alleles exo70. exo70 mutants exhibit reduced synaptic growth, locomotor activity, glutamate receptor density, mEPSP amplitude. We found that presynaptic necessary for normal growth at...
Abstract Polyglutamine (polyQ) diseases comprise Huntington’s disease and several subtypes of spinocerebellar ataxia, including ataxia type 3 (SCA3). The genomic expansion coding CAG trinucleotide sequence in genes leads to the production accumulation misfolded polyQ domain-containing proteins, which cause cellular dysfunction neuronal death. As one principal protein clearance pathways, activity ubiquitin–proteasome system (UPS) is tightly regulated ensure efficient damaged toxic proteins....
Abstract Polyglutamine (polyQ) diseases are a type of inherited neurodegenerative disorders caused by cytosine–adenine–guanine (CAG) trinucleotide expansion within the coding region disease-associated genes. We previously demonstrated that pathogenic interaction between expanded CAG RNA and nucleolin (NCL) protein triggers nucleolar stress neuronal cell death in polyQ diseases. However, mechanisms behind molecular remain unknown. Here, we report 1.45 Å crystal structure r(CAG)5 oligo...
Abstract Background CCDC88C is a ubiquitously expressed protein with multiple functions, including roles in cell polarity and the development of dendrites nervous system. Bi-allelic mutations gene cause autosomal recessive congenital hydrocephalus (OMIM #236600). Studies recently linked heterozygous to late-onset spinocerebellar ataxia type 40 #616053). Case presentation A 48-year-old Sudanese female presented pure early onset hereditary spastic paraplegia. Exome sequencing, in-silico...
The GGGGCC hexanucleotide repeat expansion mutation in the chromosome 9 open reading frame 72 (C9orf72) gene is a major genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD). In this study, we demonstrate that zinc finger (ZF) transcriptional regulator Yin Yang 1 (YY1) binds to promoter region planar cell polarity Fuzzy regulate its transcription. We show YY1 interacts with RNA via ZF interaction compromises binding FuzzyYY1 sites, resulting downregulation...
Abstract Myotonic dystrophy type 1 (DM1) is a multisystemic disorder that has been extensively studied for decades, yet our understanding of its neuropathological aspect remains rudimentary. In this study, we characterized novel model DM1 neuropathology by expressing untranslated expanded CUG repeats at the Drosophila larval neuromuscular junction. model, both pre- and postsynaptic expression participate to induce reduction synaptic boutons, increase arbor disassembly impairment locomotor...
<title>Abstract</title> MicroRNAs (miRNAs) are small non-coding RNAs responsible for RNA silencing and the posttranscriptional regulation of gene expression. Poly(A) polymerase D5 (PAPD5) catalyzes addition adenosine to 3′ end miRNAs, which promotes their subsequent degradation. In this study, we demonstrated that Yin Yang 1 (YY1) protein, a transcriptional repressor PAPD5, was recruited both foci protein aggregates, caused upregulation PAPD5 expression in Huntington’s disease (HD). We...