A5005520654- Genetic Neurodegenerative Diseases
- Autophagy in Disease and Therapy
- Mitochondrial Function and Pathology
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Metallurgical Processes and Thermodynamics
- RNA Research and Splicing
- Parkinson's Disease Mechanisms and Treatments
- Microstructure and Mechanical Properties of Steels
- Iron and Steelmaking Processes
- Endoplasmic Reticulum Stress and Disease
- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- RNA Interference and Gene Delivery
- Fungal and yeast genetics research
- Materials Engineering and Processing
- Lipid metabolism and biosynthesis
- Receptor Mechanisms and Signaling
- Amyotrophic Lateral Sclerosis Research
- Neurological disorders and treatments
- Genetics and Neurodevelopmental Disorders
- RNA modifications and cancer
- Aluminum Alloy Microstructure Properties
- Calcium signaling and nucleotide metabolism
- RNA regulation and disease
Fudan University
2016-2025
State Key Laboratory of Medical Neurobiology
2019-2025
Huashan Hospital
2006-2025
Institute of Neurobiology
2021
University of Pennsylvania
2007-2020
Shanghai Center for Brain Science and Brain-Inspired Technology
2015-2017
Massachusetts General Hospital
2014-2016
Central South University
2012-2016
State Key Laboratory of Genetic Engineering
2015-2016
Harvard University
2016
Degrading pathogenic proteins by degrader technologies such as PROTACs (proteolysis-targeting chimeras) provides promising therapeutic strategies, but selective degradation of non-protein biomolecules has been challenging. Here, we demonstrate a novel strategy to degrade autophagy-tethering compounds (ATTECs), using lipid droplets (LDs) an exemplar target. LDs are ubiquitous cellular structures storing lipids and could be degraded autophagy. We hypothesized that interacting with both the key...
Neuronal accumulation and spread of pathological α-synuclein (α-syn) fibrils are key events in Parkinson's disease (PD) pathophysiology. However, the neuronal mechanisms underlying uptake α-syn remain unclear. In this work, we identified FAM171A2 as a PD risk gene that affects aggregation. Overexpressing promotes fibril endocytosis exacerbates neurotoxicity pathology. Neuronal-specific knockdown expression shows protective effects. Mechanistically, extracellular domain 1 interacts with C...
Abstract Autophagy cargo recognition and clearance are essential for intracellular protein quality control. SQSTM1/p62 sequesters aberrant proteins mediates delivery their selective autophagic degradation. The formation of p62 non-membrane-bound liquid compartments is critical its function as a receptor. regulation phase separation/condensation has yet been poorly characterised. Using an unbiased yeast two-hybrid screening complementary approaches, we found that DAXX physically interacts...
Autophagy and ribonucleoprotein granules, such as P-bodies (PBs) stress represent vital responses to maintain cellular homeostasis. SQSTM1/p62 phase-separated droplets are known play critical roles in selective autophagy; however, it is unknown whether p62 can exist another form addition its autophagic droplets. Here, we found that, under conditions, including proteotoxicity, endotoxicity, oxidation, transformed a type of enlarged PBs, termed p62-dependent (pd-PBs). phase separation...
Most neurodegenerative diseases are linked to aberrant accumulation of aggregation-prone proteins. Among them, Huntington's disease (HD) is caused by an expanded polyglutamine repeat stretch in the N terminus mutant huntingtin protein (mHTT), which gets cleaved and aggregates brain. Recently established human induced pluripotent stem cell-derived HD neurons exhibit some disease-relevant phenotypes provide tools for research. However, they have limitations such as genetic heterogeneity...
Huntington's disease (HD) represents an important model for neurodegenerative disorders and proteinopathies. It is mainly caused by cytotoxicity of the mutant huntingtin protein (Htt) with expanded polyQ stretch. While Htt ubiquitously expressed, HD characterized selective neurodegeneration striatum. Here we report a striatal-enriched orphan G protein-coupled receptor(GPCR) Gpr52 as stabilizer in vitro vivo. modulates via cAMP-dependent but PKA independent mechanisms. located within intron...
Parkinson's disease (PD), one of the most devastating neurodegenerative brain disorders, is characterized by progressive loss dopaminergic neurons in substantia nigra (SN) and deposits α-synuclein aggregates. Currently, pharmacological interventions for PD remain inadequate. The cell necroptosis executor protein MLKL (Mixed-lineage kinase domain-like) involved various diseases, including inflammatory bowel diseases; however, its precise role remains unclear. Here, we investigated...
Increased mitochondrial damage plays a critical role in many neurodegeneration-related diseases such as Parkinson's disease (PD) and Down syndrome (DS). Thus, enhancement of degradation by small molecule compounds may provide promising new strategies to tackle these diseases. Here, we explored the strategy induce clearance mitochondria targeting them autophagy machinery autophagy-tethering (ATTECs). We provided proof-of-concept evidence demonstrating that bifunctional compound (mT1) binding...
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among elderly, and there currently no clinical treatment targeting primary impairment AMD. The earliest hallmark AMD drusen, which are yellowish spots mainly composed lipid droplets (LDs) accumulated under retinal pigment epithelium (RPE). However, potential pathogenic role this excessive LD accumulation in yet to be determined, partially due a lack chemical tools manipulate LDs specifically. Here, we...
The ability to regulate mitophagy in a living system with small molecules remains great challenge. We hypothesize that adding fragments specific the key autophagosome protein LC3 mitochondria will mimic receptor-mediated mitophagy, thus engaging autophagy-lysosome pathway induce mitochondrial degradation. Herein, we develop general biochemical approach modulate dubbed mito-ATTECs, which employ chimera composed of LC3-binding moieties linked mitochondria-targeting ligands. Mito-ATTECs trigger...