A5100747103- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Muscle Physiology and Disorders
- Neurological disorders and treatments
- Ubiquitin and proteasome pathways
- CRISPR and Genetic Engineering
- Parkinson's Disease Mechanisms and Treatments
- Amyotrophic Lateral Sclerosis Research
- Genetics and Neurodevelopmental Disorders
- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
- Prion Diseases and Protein Misfolding
- Genetics, Aging, and Longevity in Model Organisms
- Adipose Tissue and Metabolism
- Neurogenesis and neuroplasticity mechanisms
- Neurological diseases and metabolism
- Pancreatic function and diabetes
- Pluripotent Stem Cells Research
- Autism Spectrum Disorder Research
- Hereditary Neurological Disorders
- Nerve injury and regeneration
- Metabolism and Genetic Disorders
- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Neurogenetic and Muscular Disorders Research
Jinan University
2017-2025
Shanxi Provincial Institute of Chemical Industry (China)
2025
Massachusetts General Hospital
2024
University of Macau
2022-2023
Tianjin University
2020
Emory University
2010-2019
Institute of Genetics and Developmental Biology
2012-2016
Chinese Academy of Sciences
2012-2016
State Key Laboratory of Molecular Developmental Biology
2013
Kunming Medical University
2006
Huntington disease (HD) is characterized by the preferential loss of striatal medium-sized spiny neurons (MSNs) in brain. Because MSNs receive abundant glutamatergic input, their vulnerability to excitotoxicity may be largely influenced capacity glial cells remove extracellular glutamate. However, little known about role glia HD neuropathology. Here, we report that mutant huntingtin accumulates nuclei brains and decreases expression glutamate transporters. As a result, (htt) reduces uptake...
Huntington's disease (HD) is caused by polyglutamine (polyQ) expansion in huntingtin (htt), a large (350 kDa) protein that localizes predominantly to the cytoplasm. Proteolytic cleavage of mutant htt yields polyQ-containing N-terminal fragments are prone misfolding and aggregation. Disease progression HD transgenic models correlates with age-related accumulation soluble aggregated forms fragments, suggesting multiple involved selective neurodegeneration HD. Although mitochondrial dysfunction...
Huntington's disease is a neurodegenerative disorder caused by polyglutamine repeat in the Huntingtin gene (HTT). Although suppressing expression of mutant HTT (mHTT) has been explored as therapeutic strategy to treat disease, considerable efforts have gone into developing allele-specific suppression mHTT expression, given that loss Htt mice can lead embryonic lethality. It remains unknown whether depletion adult brain, regardless its allele, could be safe therapy. Here, we report permanent...
CRISPR/Cas9 has been used to genetically modify genomes in a variety of species, including non-human primates. Unfortunately, this new technology does cause mosaic mutations, and we do not yet know whether such mutations can functionally disrupt the targeted gene or pathology seen human disease. Addressing these issues is necessary if are generate large animal models diseases using CRISPR/Cas9. Here target monkey dystrophin create that lead Duchenne muscular dystrophy (DMD), recessive...
Huntington’s disease (HD) arises from the abnormal expansion of CAG repeats in huntingtin gene (HTT), resulting production mutant protein (mHTT) with a polyglutamine stretch its N-terminus. The pathogenic mechanisms underlying HD are complex and not yet fully elucidated. However, mHTT forms aggregates accumulates abnormally neuronal nuclei processes, leading to disruptions multiple cellular functions. Although there is currently no effective curative treatment for HD, significant progress...
Polyglutamine expansion causes Huntington disease (HD) and at least seven other neurodegenerative diseases. In HD, N-terminal fragments of huntingtin with an expanded glutamine tract are able to aggregate accumulate in the nucleus. Although intranuclear affects expression numerous genes, mechanism this nuclear effect is unknown. Here we report that interacts Sp1, a transcription factor binds GC-rich elements certain promoters activates corresponding genes. vitro binding immunoprecipitation...
The mechanism by which polyglutamine expansion in Huntington's disease (HD) results selective neuronal degeneration remains unclear. We previously reported that the immunohistochemical distribution of N-terminal huntingtin HD does not correspond to severity neuropathology, such significantly greater numbers aggregates are present within cortex than striatum. now show a dissociation between aggregation and pattern striatal neuron loss observed HD. Aggregate formation was predominantly spared...
Huntingtin-associated protein-1 (HAP1) was initially identified as an interacting partner of huntingtin, the Huntington disease protein. Unlike huntingtin that is ubiquitously expressed throughout brain and body, HAP1 enriched in neurons, suggesting its dysfunction could contribute to neuropathology. Growing evidence has demonstrated are anterogradely transported axons abnormal interaction between mutant may impair axonal transport. However, exact role anterograde transport remains unclear....
Neural and stem cell transplantation is emerging as a potential treatment for neurodegenerative diseases. Transplantation of specific committed neuroblasts (fetal neurons) to the adult brain provides such scientific exploration these new therapies. Huntington's disease (HD) fatal, incurable autosomal dominant (CAG repeat expansion huntingtin protein) disorder with primary neuronal pathology within caudate–putamen (striatum). In clinical trial human fetal striatal tissue transplantation, one...
Huntington's disease (HD) mouse models that express N-terminal huntingtin fragments show rapid progression and have been used for developing therapeutics. However, light microscopy reveals no significant neurodegeneration in these mice. It remains unclear how mutant induces neurodegeneration. Using caspase staining, terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling, electron microscopy, we observed N171-82Q mice, which the first 171 aa of huntingtin, displayed...
Huntington's disease (HD) is characterized by a progressive loss of neurons in the striatum and cerebral cortex caused CAG repeat expansion gene encoding huntingtin. Mice with mutation inserted into their own huntingtin (knock-in mice) are, genetically, best models human disease. Here we show for first time that knock-in mice 94 repeats develop robust early motor phenotype at 2 months age, increased rearing night. This initial increase repetitive movements was followed decreased locomotion 4...
A variety of neurological disorders and polyglutamine (polyQ) diseases are caused by misfolded proteins. The common feature these is late-onset cellular degeneration that selectively affects neurons in distinct brain regions. polyQ diseases, including Huntington's disease (HD), present a clear case selective neurodegeneration expansion-induced protein misfolding, which also leads to predominant inclusions neuronal nuclei. It remains unclear how ubiquitously expressed proteins kill neurons....
Huntington's disease (HD) is caused by the expansion of a polyglutamine tract in N-terminal region huntingtin (htt) and characterized selective neurodegeneration. In addition to forming nuclear aggregates, mutant htt accumulates neuronal processes as well synapses affects synaptic function. However, mechanism for toxicity remains be investigated. We targeted fluorescent reporters ubiquitin–proteasome system (UPS) presynaptic or postsynaptic terminals neurons. Using these biochemical assays...