A5046771718- Alzheimer's disease research and treatments
- Cholinesterase and Neurodegenerative Diseases
- Molecular Sensors and Ion Detection
- Computational Drug Discovery Methods
- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- Advanced biosensing and bioanalysis techniques
- Supramolecular Self-Assembly in Materials
- Electrochemical Analysis and Applications
- Histone Deacetylase Inhibitors Research
- Chemical Synthesis and Analysis
- Protein Structure and Dynamics
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Epigenetics and DNA Methylation
- Signaling Pathways in Disease
- Neuroscience and Neuropharmacology Research
- Biochemical and Structural Characterization
- Machine Learning in Materials Science
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Peptidase Inhibition and Analysis
- Free Radicals and Antioxidants
- Drug Transport and Resistance Mechanisms
- PARP inhibition in cancer therapy
- Analytical Chemistry and Sensors
Korea Advanced Institute of Science and Technology
2018-2025
Brigham and Women's Hospital
2024-2025
Harvard University
2024-2025
Government of the Republic of Korea
2016-2021
Daejeon University
2019-2021
Ulsan National Institute of Science and Technology
2016-2018
Abstract UM171 is a potent agonist of ex vivo human haematopoietic stem cell self-renewal 1 . By co-opting KBTBD4, substrate receptor the CUL3–RING E3 ubiquitin ligase (CRL3) complex, promotes degradation LSD1–CoREST corepressor thereby limiting attrition 2,3 However, direct target and mechanism action remain unclear. Here we show that acts as molecular glue to induce high-affinity interactions between KBTBD4 HDAC1/2 promote degradation. Through proteomics chemical inhibitor studies,...
A catecholamine neurotransmitter, dopamine (DA), is suggested to be linked the pathology of dementia; however, involvement DA and its structural analogues in pathogenesis Alzheimer's disease (AD), most common form dementia, composed multiple pathogenic factors has not been clear. Herein, we report that rationally designed derivatives (1–6) based on DA's oxidative transformation are able modulate pathological elements found AD [i.e., metal ions, metal-free amyloid-β (Aβ), metal-bound Aβ...
An amyloidogenic peptide, amyloid-β (Aβ), has been implicated as a contributor to the neurotoxicity of Alzheimer's disease (AD) that continues present major socioeconomic burden for our society. Recently, use metal complexes capable cleaving peptides arisen an efficient tactic amyloid management; unfortunately, little reported pursue this strategy. Herein, we report novel approach validate hydrolytic cleavage divalent toward two isoforms Aβ (Aβ40 and Aβ42) tune their proteolytic activity...
A simple fluorescent chemosensor 1 for the detection of Hg(2+) and pH was developed by a combination 2-aminoethyl piperazine 4-chloro-7-nitrobenz-2-oxa-1,3-diazole. The sensor showed OFF-ON behavior different colors fluorescence in presence under acidic conditions, respectively, near-perfect aqueous solution. turn-on caused inhibition photoinduced electron transfer explained theoretical calculations. could be used to quantify water samples, its vitro studies with HeLa cells Hg(2+). In...
The deposition of amyloid-β (Aβ) aggregates and metal ions within senile plaques is a hallmark Alzheimer's disease (AD). Among the modifications observed in Aβ peptides, N-terminal truncation at Phe4, yielding Aβ4–x, highly prevalent AD-affected brains significantly alters Aβ's metal-binding aggregation profiles. Despite abundance Zn(II) plaques, its impact on toxicity Aβ4–x remains unexplored. Here, we report distinct behavior N-terminally truncated Aβ, specifically Aβ4–42, absence presence...
A new turn-on fluorescent chemosensor <bold>1</bold> was developed to detect both Al<sup>3+</sup> and CN<sup>−</sup> used for practical biological applications.
Multiple pathogenic elements, including reactive oxygen species, amyloidogenic proteins, and metal ions, are associated with the development of neurodegenerative disorders. We report minimalistic redox-based principles for preparing compact aromatic compounds by derivatizing phenylene moiety various functional groups. These molecular agents display enhanced reactivities against multiple targets such as free radicals, metal-free amyloid-β (Aβ), metal-bound Aβ that implicated in most common...
Cancer mutations can create neomorphic protein-protein interactions to drive aberrant function 1 . As a substrate receptor of the CULLIN3-RBX1 E3 ubiquitin ligase complex, KBTBD4 is recurrently mutated in medulloblastoma (MB) 2 , most common embryonal brain tumor children, and pineoblastoma 3 These impart gain-of-function induce degradation transcriptional corepressor CoREST 4 However, their mechanism action remains unresolved. Here, we elucidate mechanistic basis by which promote through...
Bilirubin (BR) is a de novo synthesized metabolite of human cells. However, subcellular localization BR in the different organelles cells has been largely unknown. Here, utilizing UnaG as genetically encoded fluorescent sensor, we report existence relatively BR-enriched and BR-depleted microspaces various cellular live Our studies indicate that (i) cytoplasmic facing membrane endoplasmic reticulum (ER) nucleus are spaces (ii) mitochondrial intermembrane space ER lumen spaces. Thus,...
The complex and multifaceted pathology of Alzheimer's disease (AD) continues to present a formidable challenge the establishment long-term treatment strategies. Multifunctional compounds able modulate reactivities various pathological features, such as amyloid-β (Aβ) aggregation, metal ion dyshomeostasis, oxidative stress, have emerged useful tactic. Recently, an incorporation approach rational design multipurpose small molecules has been validated through production multifunctional ligand...
Reversible modification of the histone H3 N-terminal tail is critical in regulating chromatin structure, gene expression, and cell states, while its dysregulation contributes to disease pathogenesis. Understanding crosstalk between modifications nucleosomes constitutes a central challenge epigenetics. Here, we describe an engineered sortase transpeptidase, cW11, that displays highly favorable properties for introducing scarless tails onto nucleosomes. This approach significantly accelerates...
We illuminate that cytochrome c (Cyt ) directly interacts with amyloid-β (Aβ) and alters Aβ amyloidogenesis in a peroxide-dependent manner, which demonstrates its new role towards the amyloid pathology associated Alzheimer's disease.
Abstract Intracellular C ‐terminal cleavage of the amyloid precursor protein (APP) is elevated in brains Alzheimer's disease (AD) patients and produces a peptide labeled APP‐C31 that suspected to be involved pathology AD. But details about role development are not known. Here, this work reports directly interacts with N self‐recognition regions amyloid‐β 40 (Aβ ) form transient adducts, which facilitates aggregation both metal‐free metal‐bound Aβ peptides aggravates their toxicity....
Despite their unique advantages, the full potential of molecular probes for fluorescent monitoring amyloid-β (Aβ) aggregates has not been fully exploited. This limited utility stems from lack knowledge about hydrophobic interactions between molecules Aβ probes, as well those probe and aggregate. Herein, we report first mechanistic study, which firmly establishes a structure–signaling relationship probes. We synthesized series five based on an archetypal donor–acceptor–donor scaffold (denoted...
A novel series of 1,10-phenanthroline (phen) derivatives capable regulating acid sphingomyelinase, Zn(<sc>ii</sc>)-bound amyloid-β, or both was rationally designed.