A5001317899- Cholesterol and Lipid Metabolism
- Peroxisome Proliferator-Activated Receptors
- Cancer, Lipids, and Metabolism
- Lipid metabolism and biosynthesis
- Endoplasmic Reticulum Stress and Disease
- Lipoproteins and Cardiovascular Health
- Ubiquitin and proteasome pathways
- Lipid Membrane Structure and Behavior
- Neuroscience and Neuropharmacology Research
- Lysosomal Storage Disorders Research
- Neurogenesis and neuroplasticity mechanisms
- Epigenetics and DNA Methylation
- Cellular transport and secretion
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Hedgehog Signaling Pathway Studies
- Amino Acid Enzymes and Metabolism
- Metabolism and Genetic Disorders
- Adipokines, Inflammation, and Metabolic Diseases
- Mitochondrial Function and Pathology
- Sleep and Wakefulness Research
- 14-3-3 protein interactions
- Memory and Neural Mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Receptor Mechanisms and Signaling
- Protein Degradation and Inhibitors
Wuhan University
2015-2024
Kunming Medical University
2019-2023
First Affiliated Hospital of Kunming Medical University
2019-2023
Beijing Anding Hospital
2022
Capital Medical University
2022
First Affiliated Hospital of University of South China
2021
University of South China
2021
Chongqing University of Arts and Sciences
2021
First Hospital of Shanxi Medical University
2018
Shanxi Medical University
2018
In the adult mouse brain, subventricular zone (SVZ) is a neurogenic stem cell niche only 4-5 diameters thick. Within this narrow zone, unique microenvironment supports self-renewal, gliogenesis or neurogenesis lineage decisions and tangential migration of newly generated neurons out SVZ into olfactory bulb. However, with aging, declines. Here, we examine dynamic interplay between cytoarchitecture through aging. Assembly high-resolution electron microscopy images corresponding coronal...
Statins are inhibitors of HMG-CoA reductase, the rate-limiting enzyme cholesterol biosynthesis, and have been clinically used to treat cardiovascular disease. However, a paradoxical increase reductase protein following statin treatment may attenuate effect side effects. Here we present previously unexplored strategy alleviate statin-induced accumulation by inducing its degradation. Inspired observations that intermediates trigger degradation, identify potent degrader, namely Cmpd 81, through...
A missing link in cholesterol absorption Cholesterol is important for general health, but too much can build up artery walls and cause cardiovascular disease. Low-density lipoprotein (LDL-C) often referred to as “bad cholesterol”; keeping LDL-C within stringent limits recommended reduce the risk of heart attack stroke. Zhang et al. discovered that some individuals have an inherited frameshift mutation LIMA1 gene (also known EPLIN or SREBP3 ). The has not been linked lipid metabolism before,...
Sterol-regulated HMG-CoA reductase (HMGCR) degradation and SREBP-2 cleavage are two major feedback regulatory mechanisms governing cholesterol biosynthesis. Reportedly, lanosterol selectively stimulates HMGCR degradation, is a specific regulator of cleavage. However, it unclear whether other endogenously generated sterols regulate these events. Here, we investigated the sterol intermediates from mevalonate pathway biosynthesis using CRISPR/Cas9-mediated genetic engineering approach. With...
High blood cholesterol accelerates the progression of atherosclerosis, which is an asymptomatic process lasting for decades. Rupture atherosclerotic plaques induces thrombosis, results in myocardial infarction or stroke. Lowering levels beneficial preventing cardiovascular disease. Low-density lipoprotein (LDL) receptor (LDLR) was used as bait to identify its binding proteins plasma, and coagulation factor prekallikrein (PK; encoded by KLKB1 gene) revealed. The correlation between serum PK...
The subventricular zone (SVZ) of the adult mouse brain is a narrow stem cell niche that lies along length lateral wall ventricles. SVZ supports neurogenesis throughout adulthood; however, with increasing age, ventral deteriorates and only dorsolateral remains neurogenic. Associated elderly SVZ, we reported previously an increased number astrocytes interposed within adjacent ependymal lining. Here, show integrated ependyma are dividing, BrdU-labeled share cellular adherens neighboring cells....
The cyclic adenosine monophosphate (cAMP), mitogen-activated protein kinase (MAPK), and cAMP response element-binding (CREB) transcriptional pathway is required for consolidation of hippocampus-dependent memory. In mice, this undergoes a circadian oscillation memory persistence that reaches peak during the daytime. Because mice exhibit polyphasic sleep patterns day, suggested interesting possibility cAMP, MAPK activity, CREB phosphorylation may be elevated sleep. Here, we report...
Obesity is a critical risk factor for hepatocellular carcinoma (HCC). However, it remains unknown whether inhibition of de novo lipid biosynthesis can suppress HCC. In this study, we blocked the sterol regulatory element‐binding protein (SREBP) pathway, one key determinants homeostasis, by ablating 78‐kDa cell‐surface glycoprotein or SREBP cleavage‐activating in hepatocytes, as well administering chemical compound called betulin. We found that either genetically pharmacologically inhibiting...
The transport of LDL-derived cholesterol from lysosomes to peroxisomes is facilitated by membrane contacts formed between the lysosomal protein synaptotagmin VII and peroxisomal lipid phosphatidylinositol 4, 5-bisphosphate [PI(4,5)P2]. Here, we used RNA interference search for regulators PI(4,5)P2 study effects altered homeostasis on transport. We found that knockdown 5-phosphate 4-kinase type-2 α (PIP4K2A) reduced levels, decreased lysosome-peroxisome contacts, increased accumulation in...
Niemann-Pick C1-like 1 (NPC1L1) is essential for intestinal cholesterol absorption. Together with the cholesterol-rich and Flotillin-positive membrane microdomain, NPC1L1 internalized via clathrin-mediated endocytosis transported to endocytic recycling compartment (ERC). When ERC level decreases, interacts LIMA1 moves back plasma membrane. However, how leaves unknown. Here, we find that, in male mice, intracellular bile acids facilitate transport other organelles, such as endoplasmic...
Proper intracellular cholesterol trafficking is critical for cellular function. Two lysosome-resident proteins, NPC1 and NPC2, mediate the egress of low-density lipoprotein-derived from lysosomes. However, other proteins involved in this process remain largely unknown. Through amphotericin B-based selection, we isolated two transport-defective cell lines. Subsequent whole-transcriptome-sequencing analysis revealed lines bearing same mutation vacuolar protein sorting 53 (Vps53) gene....
Niemann-Pick type C (NPC) disease is a fatal inherited neurodegenerative disorder caused by loss-of-function mutations in the NPC1 or NPC2 gene. There no effective way to treat NPC disease. In this study, we used adeno-associated virus (AAV) serotype 9 (AAV9) deliver functional gene systemically into NPC1−/− mice at postnatal day 4. One single AAV9-NPC1 injection resulted robust expression various tissues, including brain, heart, and lung. Strikingly, AAV9-mediated delivery significantly...