A5005926903- Alzheimer's disease research and treatments
- Chemical Synthesis and Analysis
- Parkinson's Disease Mechanisms and Treatments
- interferon and immune responses
- Click Chemistry and Applications
- Viral Infections and Vectors
- RNA Research and Splicing
- Mosquito-borne diseases and control
- Lysosomal Storage Disorders Research
- Genetic Neurodegenerative Diseases
- Peptidase Inhibition and Analysis
- Carbohydrate Chemistry and Synthesis
- Cerebrovascular and Carotid Artery Diseases
- Cancer-related gene regulation
- Immune Response and Inflammation
- Protein Structure and Dynamics
- 14-3-3 protein interactions
- Virus-based gene therapy research
- Lipid metabolism and biosynthesis
- Computational Drug Discovery Methods
- Nuclear Structure and Function
- Synthesis and Catalytic Reactions
- Prion Diseases and Protein Misfolding
- Neuroblastoma Research and Treatments
- RNA modifications and cancer
Tsinghua University
2020-2024
Anshun University
2019
Significance Posttranslational modifications (PTMs) play an important role in modulating α-syn structure, function, and pathology. Phosphorylation commonly applies to pathological aggregation Lewy bodies is a hallmark of Parkinson’s disease (PD). Here, we obtain homogeneous fibrils formed by semisynthesized with site-specific phosphorylation at Y39. The synthetic fibril recapitulates the neuropathology degradation resistance endogenous pY39 PD. Cryo-EM structure determination reveals fold...
Abstract α-Synuclein forms amyloid fibrils that are critical in the progression of Parkinson’s disease and serves as pathological hallmark this condition. Different posttranslational modifications have been identified at multiple sites α-synuclein, influencing its conformation, aggregation function. Here, we investigate how disease-related phosphorylation O-GlcNAcylation same α-synuclein site (S87) affect fibril structure neuropathology. Using semi-synthesis, obtained homogenous monomer with...
The aggregation of α-Synuclein (α-Syn) into amyloid fibrils is the hallmark Parkinson's disease. Under stress or other pathological conditions, accumulation α-Syn oligomers main contributor to cytotoxicity. A potential approach for treating disease involves preventing these oligomers. In this study, we present a novel mechanism involving conserved group disorderly proteins known as small EDRK-rich factor (SERF), which promotes through cophase separation process. Using diverse methods like...
Tau plays a major role in Alzheimer's disease (AD) and several other neurodegenerative diseases. undergoing liquid–liquid phase separation (LLPS) performs specific physiological functions, induces pathological processes, contributes to neurodegeneration. Regulating helps maintain functions of inhibits aggregation. Here, we show that the 14-3-3 zeta isoform (14-3-3ζ) participates LLPS. 14-3-3ζ can undergo co-phase with WT Tau, participate stabilize droplets, inhibit droplet-driven tubulin...
The stimulator of interferon genes (STING) pathway is a potent therapeutic target for innate immunity. Despite the efforts to develop pocket-dependent small-molecule STING agonists that mimic endogenous ligand, cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), most these showed disappointing results in clinical trials owing limitations pocket. In this study, we developed novel pocket-independent STING-activating (piSTINGs), which act through multivalency-driven oligomerization...
A chemoselective peptide and protein modification strategy of dehydroalanine (Dha) specifically reacting with phosphines for attachment different functional groups.
Glycation regulates co-phase separation of K9/R9 peptides and RNA by attenuating electrostatic interactions increasing hydrophobic interactions.
Lysine-specific peptide and protein modification strategies are widely used to study charge-related functions applications. However, these often result in the loss of positive charge on lysine, significantly impacting properties proteins. Herein, we report a strategy preserve selectively convert amines lysine side chains amidines using nitriles hydroxylamine under aqueous conditions. Various unprotected peptides proteins were successfully modified with high conversion rate. Moreover,...
Abstract Lysine‐specific peptide and protein modification strategies are widely used to study charge‐related functions applications. However, these often result in the loss of positive charge on lysine, significantly impacting properties proteins. Herein, we report a strategy preserve selectively convert amines lysine side chains amidines using nitriles hydroxylamine under aqueous conditions. Various unprotected peptides proteins were successfully modified with high conversion rate....
Abstract The stimulator of interferon genes (STING) pathway is a potent therapeutic target for innate immunity. Despite the efforts to develop pocket‐dependent small‐molecule STING agonists that mimic endogenous ligand, cyclic guanosine monophosphate–adenosine monophosphate (cGAMP), most these showed disappointing results in clinical trials owing limitations pocket. In this study, we developed novel pocket‐independent STING‐activating (piSTINGs), which act through multivalency‐driven...
Assessment of the value three-dimensional digital subtraction angiography (3D-DSA) combined with neurointerventional thrombolysis in treatment senile cerebrovascular occlusion was investigated. A total 129 patients admitted to Affiliated Hospital Zunyi Medical University from August 2015 September 2017 were collected. Among them, 69 who underwent catheter under 3D-DSA included study group, and 60 treated control group. The levels inflammatory cytokines IL-6, IL-1β IL-8 two groups measured by...
ABSTRACT α-Synuclein (α-syn) forms amyloid fibrils that are critical in the progression of Parkinson’s disease (PD) and serves as pathological hallmark PD. Different posttranslational modifications (PTMs) have been identified at multiple sites α-syn, influencing its conformation, aggregation function. Here, we investigate how disease-related phosphorylation O-GlcNAcylation same α-syn site (S87) affect fibril structure neuropathology. Using semi-synthesis, obtained homogenous monomer with...
Abstract Post-translational modifications (PTMs) of α-synuclein (α-syn), e.g. phosphorylation, play an important role in modulating α-syn pathology Parkinson’s disease (PD) and α-synucleinopathies. Accumulation phosphorylated fibrils Lewy bodies neurites is the histological hallmark these diseases. However, it unclear how phosphorylation relates to pathology. Here, by combining chemical synthesis bacterial expression, we obtained homogeneous with site-specific at Y39, which exhibits enhanced...
Considering the fact that site-selective late-stage diversification of peptides and proteins remains a challenge for biochemistry, strategies targeting low-abundance natural amino acids need to be further developed. As an extremely oxidation-sensitive acid, methionine emerges as promising target chemo- modification. Herein we report efficient highly selective modification on residues by one-pot O- N-transfer reaction, generating sulfoximine-modified with near-perfect conversion within 10...