A5038034894- Alzheimer's disease research and treatments
- Cholinesterase and Neurodegenerative Diseases
- Computational Drug Discovery Methods
- Neuroscience and Neuropharmacology Research
- Supramolecular Self-Assembly in Materials
- Tryptophan and brain disorders
- Synthesis and Reactivity of Heterocycles
- Neuroinflammation and Neurodegeneration Mechanisms
- Nuclear Receptors and Signaling
- Glaucoma and retinal disorders
- Functional Brain Connectivity Studies
- Medicinal Plants and Neuroprotection
- Graph theory and applications
- Receptor Mechanisms and Signaling
- Dementia and Cognitive Impairment Research
- Prion Diseases and Protein Misfolding
- Chemical Synthesis and Analysis
Yonsei University
2019-2024
Incheon National University
2024
Abstract Amyloid-β (Aβ) oligomers are implicated in the onset of Alzheimer’s disease (AD). Herein, quinoline-derived half-curcumin-dioxaborine (Q-OB) fluorescent probe was designed for detecting Aβ by finely tailoring hydrophobicity biannulate donor motifs donor-π-acceptor structure. Q-OB shows a great sensing potency dynamically monitoring oligomerization during amyloid fibrillogenesis vitro. In addition, we applied this strategy to fluorometrically analyze self-assembly kinetics...
We compared levels of Aβ by self-standard in plasma using an interdigitated microelectrode sensor to detect Alzheimer disease.
Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by the formation of toxic amyloid-β (Aβ) oligomers and plaques. Considering that Aβ misfolding aggregation precedes development cognitive impairment in AD, investigating therapeutic means clearance pre-existing aggregates shows promise as viable disease-modifying treatment. Here, we report small molecule, necrostatin-1 (Nec-1), reduces back to non-toxic monomers vitro vivo . Intravenous administration...
Rhizolutin (1) was discovered as a natural product of ginseng-rhizospheric Streptomyces sp. WON17. Its structure features an unprecedented 7/10/6-tricyclic dilactone carbon skeleton composed dimethylcyclodecatriene flanked by 7-membered and 6-membered lactone ring based on spectroscopic analysis. During unbiased screening libraries, this novel compound found to dissociate amyloid-β (Aβ) plaques tau tangles, which are key pathological hallmarks Alzheimer's disease (AD). treatment APP/PS1...
Alzheimer’s disease (AD) is an ageing-related neurodegenerative characterized and diagnosed by deposition of insoluble amyloid-β (Aβ) plaques in the brain. The plaque accumulation brain directly affects reduced levels Aβ cerebrospinal fluid (CSF) blood, as can freely transport blood-brain barrier, clinical investigations have suggested these two biofluids promising samples for vitro diagnosis. Given that human eye structurally resembles often observed ocular region AD patients, this study,...
Amyloid-β (Aβ) oligomers are implicated in Alzheimer disease (AD). However, their unstable nature and heterogeneous state disrupts elucidation of explicit role AD progression, impeding the development tools targeting soluble Aβ oligomers. Herein parallel anti-parallel variants Aβ(1-40) dimers were designed synthesized, pathogenic properties models characterized. Anti-parallel induced cognitive impairments with increased amyloidogenesis cytotoxicity, this dimer was then used a screening...
Cerebral amyloid-β (Aβ) deposition is a representative hallmark of Alzheimer's disease (AD). Development Aβ-clearing small molecules could be an advantageous therapeutic strategy for Aβ clearance considering the advantages in terms side effects, cost-effectiveness, stability, and oral bioavailability. Here, we report Aβ-dissociating molecule, YIAD-0121, derivative 4-acyl-3,4-dihydropyrrolo[1,2-a]pyrazine. Through series anti-Aβ screening assays, YIAD-0121 was identified to inhibit...
Abnormal assembly of amyloid β (Aβ) in the brain is implicated Alzheimer's disease (AD) and associated with cognitive impairments. Since Aβ accumulation occurs advance onset clinical symptoms, identifying preventable drug candidates regulating regarded as a promising approach AD therapeutic. Herein, we synthesized eight Yonsei Institute pharmaceutical sciences Drug (YIAD) compounds based on 5-benzyl-6-phenylbenzo[4,5]imidazo[1,2-a]pyrrolo[2,1-c]pyrazine structures. Subsequently, YIAD-0203...
Abstract Amyloid‐β (Aβ) in the form of neurotoxic aggregates is regarded as main pathological initiator and key therapeutic target Alzheimer's disease. However, anti‐Aβ drug development has been impeded by lack a needed for structure‐based design low permeability blood–brain barrier (BBB). An attractive strategy amyloid‐based peptidomimetics that exploit self‐assembling nature Aβ penetrate BBB. Herein, we designed dimeric peptide candidate based on N‐terminal fragment Aβ, DAB, found to cross...
Aggregated amyloid-β (Aβ) is considered a pathogenic initiator of Alzheimer's disease (AD), in strong association with tau hyperphosphorylation, neuroinflammation, synaptic dysfunction, and cognitive decline. As the removal amyloid burden from AD patient brains by antibodies has shown therapeutic potential, development small molecule drugs inducing chemical dissociation clearance Aβ compelling as strategy. In this study, we synthesized screened aryloxypropanolamine derivatives identified...
Aggregation of misfolded amyloid-β (Aβ) and hyperphosphorylated tau proteins to plaques tangles, respectively, is the major drug target Alzheimer's disease (AD), as former an onset biomarker latter associated with neurodegeneration. Thus, we report a small molecule candidate, DN5355, dual-targeting function toward aggregates both Aβ tau. DN5355 was selected through series four screenings assessing 52 chemicals for their functions inhibit reverse aggregation by utilizing thioflavin T. When...
Comprehending early amyloidogenesis is essential for the development of effective therapeutic strategies. In tauopathies like Alzheimer’s disease (AD), abnormal accumulation tau protein initiated by pathological seeds. Mounting evidence implies that microtubule binding domain, consisting three to four repeats, plays a pivotal role in this process, yet exact region driving formation pathogenic species needs be further scrutinized. Here, we chemically synthesized individual repeats identify...
Comprehending early amyloidogenesis is essential for the development of effective therapeutic strategies. In tauopathies like Alzheimer’s disease (AD), abnormal accumulation tau protein initiated by pathological seeds. Mounting evidence implies that microtubule binding domain, consisting three to four repeats, plays a pivotal role in this process, yet exact region driving formation pathogenic species needs be further scrutinized. Here, we chemically synthesized individual repeats identify...
Amyloid-β (Aβ) aggregated forms are highly associated with the onset of Alzheimer's disease (AD). Aβ abnormally accumulates in brain and induces neuronal damages symptoms AD such as cognitive impairment memory loss. Since an antibody drug, aducanumab, reduces aggregates delays clinical decline, clearance accumulated is accounted a therapeutic approach to treat AD. In this study, we synthesized 17 benzofuran derivatives that may disaggregate oligomers plaques into inert monomers. By series...
Alzheimer disease (AD) is a neurodegenerative disorder characterized by the aberrant production and accumulation of amyloid-β (Aβ) peptides in brain. Accumulated Aβ soluble oligomer insoluble plaque forms are considered to be pathological culprit biomarker disorder. Here, we report fluorescent universal Aβ-indicator YI-13, 5-(4-fluorobenzoyl)-7,8-dihydropyrrolo[1,2-b]isoquinolin-9(6H)-one, which detects monomers, dimers, plaques. We synthesized library 26 fluorescence chemicals with...
Abstract Rhizolutin ( 1 ) was discovered as a natural product of ginseng‐rhizospheric Streptomyces sp. WON17. Its structure features an unprecedented 7/10/6‐tricyclic dilactone carbon skeleton composed dimethylcyclodecatriene flanked by 7‐membered and 6‐membered lactone ring based on spectroscopic analysis. During unbiased screening libraries, this novel compound found to dissociate amyloid‐β (Aβ) plaques tau tangles, which are key pathological hallmarks Alzheimer's disease (AD). treatment...
Indolizino[3,2- c ]quinoline derivatives are potential imaging agents targeting various forms of amyloid-β plaques.
Abstract Amyloid‐β (Aβ) oligomers are implicated in Alzheimer disease (AD). However, their unstable nature and heterogeneous state disrupts elucidation of explicit role AD progression, impeding the development tools targeting soluble Aβ oligomers. Herein parallel anti‐parallel variants Aβ(1–40) dimers were designed synthesized, pathogenic properties models characterized. Anti‐parallel induced cognitive impairments with increased amyloidogenesis cytotoxicity, this dimer was then used a...
Abstract Background Alzheimer’s disease (AD) is predominantly caused by the aggregation of amyloid‐β (Aβ) peptides into neurotoxic plaques. Current therapeutic approaches using monoclonal antibodies, like aducanumab and lecanemab, have shown promise in reversing Aβ aggregation. However, these treatments are expensive challenging to administer. Small molecules offer a more accessible alternative but face specificity hurdles. Our study explores library hybrid compounds, integrating structures...
Abstract Background The accumulation of amyloidogenic proteins is recognized as a primary biomarker, initiator pathology, and potential therapeutic target for Alzheimer’s disease (AD). An unbiased screening small molecule library was conducted to identify new chemical compounds exhibiting amyloid‐dissociative properties. Method ability aryloxypropanolamine derivatives dissociate amyloid‐β (Aβ) aggregates evaluated through in vitro assays. Subsequent assessments involved immunostaining,...
Abstract Amyloid-β oligomers ( o Aβ) are implicated in the onset of Alzheimer’s disease (AD). Herein, quinoline-derived half-curcumin-dioxaborine Q-OB ), a highly selective and sensitive fluorescent probe, was designed for detecting Aβ by finely tailoring amphiphilicity biannulate donor motifs D-π-A structure. shows great sensing potency dynamically monitoring during amyloid fibrillogenesis vitro vivo . For first time, we applied this strategy to fluorometrically analyze self-assembly...
Abstract Amyloid‐β (Aβ) in the form of neurotoxic aggregates is regarded as main pathological initiator and key therapeutic target Alzheimer's disease. However, anti‐Aβ drug development has been impeded by lack a needed for structure‐based design low permeability blood–brain barrier (BBB). An attractive strategy amyloid‐based peptidomimetics that exploit self‐assembling nature Aβ penetrate BBB. Herein, we designed dimeric peptide candidate based on N‐terminal fragment Aβ, DAB, found to cross...
Abstract Background Alzheimer’s disease (AD) is characterized by the aggregation of amyloid‐β (Aβ) and tau, leading to neuronal cell death, neuroinflammation, brain atrophy. As Aβ tau aggregates are observed in decades before onset cognitive symptoms, clearance these has been widely accepted for AD treatments. Method Through unbiased screening against natural product libraries, rhizolutin was selected its regulatory effects on were validated thioflavin T assays. Clearance plaques APP/PS1...