A5053105669- Alzheimer's disease research and treatments
- Ubiquitin and proteasome pathways
- interferon and immune responses
- Drug Transport and Resistance Mechanisms
- Immune Response and Inflammation
- Computational Drug Discovery Methods
- bioluminescence and chemiluminescence research
- Biochemical and Molecular Research
- Protein Structure and Dynamics
- Alkaline Phosphatase Research Studies
- Peptidase Inhibition and Analysis
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Retinoids in leukemia and cellular processes
- Cytomegalovirus and herpesvirus research
- Genetics and Neurodevelopmental Disorders
- HIV Research and Treatment
- Insect and Pesticide Research
- Protein Degradation and Inhibitors
- Neuroinflammation and Neurodegeneration Mechanisms
- Advanced Biosensing Techniques and Applications
- Photoreceptor and optogenetics research
- Cholinesterase and Neurodegenerative Diseases
- Viral Infections and Vectors
- Endoplasmic Reticulum Stress and Disease
- Advanced biosensing and bioanalysis techniques
Sun Yat-sen University
2017-2025
Abstract Cyclic GMP-AMP synthase (cGAS) is an essential sensor of aberrant cytosolic DNA for initiating innate immunity upon invading pathogens and cellular stress, which considered as a potential drug target autoimmune autoinflammatory diseases. Here, we report the discovery class cyclopeptide inhibitors cGAS identified by in vitro screening assay from focused library cyclic peptides. These cyclopeptides specifically bind to binding site block dsDNA with cGAS, subsequently inhibit...
Abstract The magnitude of Type I interferon (IFN) mediated innate immune response within the tumor microenvironment (TME) critically influences effectiveness radiotherapy. Unfortunately, due to a myriad resistance mechanisms, double‐stranded DNA (dsDNA) signals produced by cells postradiotherapy often induce diminished from cells. Through chemical screening targeting deubiquitinating enzymes, we identified USP1 (Ubiquitin Specific Peptidase 1) inhibitor as an enhancer post‐radiotherapy dsDNA...
Stabilizing the monomeric amyloid-β peptide by tyrocidine A prevents accumulation of oligomers.
The first proteolysis targeting chimeras for the intracellular elimination of transforming growth factor-β1 (TGF-β1), which contributes to various diseases, is described.
Elimination of amyloid-β (Aβ) oligomers remains challenging. We describe here a novel strategy to prevent and eliminate the Aβ from either early aggregation or fibril dissolution pathway by targeting flexible N-terminus, but not widely investigated hydrophobic segment, with rationally designed cyclopeptide.
The intrinsic haemolysis of an amyloid-β (Aβ) N-terminal targeting gramicidin S derivative was successfully dissociated from its Aβ oligomer-preventing activities via Ala-scanning-based regulation molecular amphiphilicity. representative analogue DGR-7 shows low toxicity but significant efficiency in preventing oligomers and reducing amyloid plaques APP/PS1 transgenic AD mice.
Raloxifene, a selective estrogen receptor modulator, displays benefits for Alzheimer's disease (AD) prevention in postmenopausal women as hormonal changes during menopause have the potential to influence AD pathogenesis, but underlying mechanism of its neuroprotection is not entirely clear. In this study, effects raloxifene on amyloid-β (Aβ) amyloidogenesis were evaluated. The results demonstrated that inhibits Aβ42 aggregation and destabilizes preformed fibrils through directly interacting...
Abstract Pyroglutamate (pE)‐modified amyloid‐β (Aβ) peptides play a crucial role in the development of Alzheimer's disease. pEAβ 3‐42 can rapidly form oligomers that gradually elongate hydrophobic segments to β‐sheet‐rich amyloid intermediates, ultimately resulting formation mature fibrils. also catalyze aggregation Aβ species and subsequently accelerate senile plaques. Considering recent clinical success ‐targeting antibody donanemab, molecules strongly bind prevent its catalytic effect on...
Abstract Bioluminogenic probes emerged as powerful tools for imaging and analysis of various bioanalyses, but traditional approaches would be limited to the low sensitivity during determine activity protease in clinical specimens. Herein, we proposed a caged luciferase inhibitor‐based bioluminescence‐switching strategy (CLIBS) by using cleavable inhibitor modulate reporter amplify detective signals, which led enhancement detection sensitivity, enabled determination circulating Aminopeptidase...
The extensive applications of Firefly luciferase (Fluc) in numerous biological, biomedical, and clinical investigations rendered an urgent need for efficient biocompatible Fluc inhibitors the construction novel assay platforms. Herein we describe identification 2-benzylidene-tetralone derivatives as highly potent reversible by competing with d-luciferin. most active compound 48 was found to have >7000 fold higher potency (IC50 = 0.25 nM) than that well-known inhibitor resveratrol 1.9 μM)...