A5101443118- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Heat shock proteins research
- Muscle Physiology and Disorders
- Ferroptosis and cancer prognosis
- Air Quality and Health Impacts
- Immune cells in cancer
- Neurological disorders and treatments
- Adipose Tissue and Metabolism
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Hereditary Neurological Disorders
- Neurogenesis and neuroplasticity mechanisms
- CRISPR and Genetic Engineering
- Fungal and yeast genetics research
- Ubiquitin and proteasome pathways
- Neuroinflammation and Neurodegeneration Mechanisms
Weifang Medical University
2022
Emory University
2014-2020
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...
In the brain, astrocytes secrete diverse substances that regulate neuronal function and viability. Exosomes, which are vesicles produced through formation of multivesicular bodies their subsequent fusion with plasma membrane, also released from via exocytotic secretion. Astrocytic exosomes carry heat shock proteins can reduce cellular toxicity misfolded prevent neurodegeneration. Although mutant huntingtin (mHtt) affects multiple functions astrocytes, it remains unknown whether mHtt impairs...
Brain-derived neurotrophic factor (BDNF) is essential for neuronal differentiation and survival. We know that BDNF levels decline in the brains of patients with Huntington9s disease (HD), a neurodegenerative caused by expression mutant huntingtin protein (mHtt), furthermore administration HD mice protective against neuropathology. produced neurons, but astrocytes are also an important source brain. Nonetheless, whether mHtt affects astrocytic brain remains unknown. Here we investigated from...
Significance It remains unclear why astrocytes are affected to a lesser extent than neurons in variety of neurodegenerative diseases. We report the higher activity C terminus Hsp70-interacting protein (CHIP), cochaperone Hsp70, neurons, which not only promotes degradation misfolded proteins, but also upregulates levels basal and stress-induced Hsp70 astrocytes. Furthermore, low CHIP is caused by abundant expression HspBP1, an inhibitor CHIP. Knocking down HspBP1 prevents accumulation...
In neurodegenerative diseases caused by misfolded proteins, including Huntington9s disease (HD), the neuronal processes and terminals are particularly prone to accumulation of leading axonal synaptic dysfunction. This compartment-dependent can result from either altered transport proteins or impaired protein degradation. Mutant huntingtin (mHtt), HD protein, is known affect intracellular be degraded proteasome autophagy, but how mHtt accumulates in processes, an early pathological event...
Although misfolded proteins are ubiquitinated and cleared by the proteasome, they can accumulate in synapses aged neurons to promote synaptic dysfunction a variety of neurodegenerative diseases, including Huntington's disease (HD), which is caused polyglutamine expansion huntingtin. The mechanism behind this aging-related phenomenon unknown has been difficult investigate using animals with short life spans. With brain tissues from longer-lived rhesus monkeys different ages, we found that...
Article9 April 2020Open Access Source DataTransparent process Phosphorylation of myelin regulatory factor by PRKG2 mediates demyelination in Huntington's disease Peng Yin Corresponding Author [email protected] orcid.org/0000-0002-4811-6956 Ministry Education CNS Regeneration Collaborative Joint Laboratory, Guangdong-Hongkong-Macau Institute Regeneration, Jinan University, Guangzhou, China Department Human Genetics, Emory University School Medicine, Atlanta, GA, USA Search for more papers...
The Huntington's disease (HD) protein, huntingtin (HTT), is a large protein consisting of 3144 amino acids and has conserved N-terminal sequences that are followed by polyglutamine (polyQ) repeat. Loss Htt known to cause embryonic lethality in mice, whereas polyQ expansion leads adult neuronal degeneration. Whether HTT essential for development or contributes only late-onset neurodegeneration remains unknown. We established knock-in mice (N160Q-KI) expressing the first 208 with 160Q, they...