A5022181614- Parkinson's Disease Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Adipose Tissue and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Nuclear Receptors and Signaling
- Neurological disorders and treatments
- Peptidase Inhibition and Analysis
- Protease and Inhibitor Mechanisms
- Lysosomal Storage Disorders Research
- IL-33, ST2, and ILC Pathways
- Mitochondrial Function and Pathology
- Neurological diseases and metabolism
- Metabolism, Diabetes, and Cancer
- Epigenetics and DNA Methylation
- PARP inhibition in cancer therapy
- DNA Repair Mechanisms
- Layered Double Hydroxides Synthesis and Applications
- Electromagnetic Fields and Biological Effects
- NF-κB Signaling Pathways
- Autophagy in Disease and Therapy
- Peroxisome Proliferator-Activated Receptors
- Botulinum Toxin and Related Neurological Disorders
- RNA regulation and disease
- Genetic Neurodegenerative Diseases
- Cell Adhesion Molecules Research
Seoul National University
2016-2024
University of California, Berkeley
2020-2024
Yonsei University
2013-2024
Convergence Research Center for Diagnosis Treatment and Care System of Dementia
2023
Convergence
2023
New Generation University College
2021-2022
Masan University
2021
Korea National Sport University
2021
Konkuk University
2014-2021
German Center for Neurodegenerative Diseases
2021
Parkinson's disease (PD) and Multiple System Atrophy (MSA) are clinically distinctive diseases that feature a common neuropathological hallmark of aggregated α-synuclein. Little is known about how differences in α-synuclein aggregate structure affect phenotype. Here, we amplified aggregates from PD MSA brain extracts analyzed the conformational properties using fluorescent probes, NMR spectroscopy electron paramagnetic resonance. We also generated several vitro polymorphs. found...
Abstract A single amyloidogenic protein is implicated in multiple neurological diseases and capable of generating a number aggregate “strains” with distinct structures. Among the proteins, α-synuclein generates patterns proteinopathies group diseases, such as Parkinson disease (PD), dementia Lewy bodies (DLB), system atrophy (MSA). However, link between specific conformations pathologies, key concept strain hypothesis, remains elusive. Here we show that presence bacterial endotoxin,...
We utilized human midbrain-like organoids (hMLOs) generated from pluripotent stem cells carrying glucocerebrosidase gene (GBA1) and α-synuclein (α-syn; SNCA) perturbations to investigate genotype-to-phenotype relationships in Parkinson disease, with the particular aim of recapitulating α-syn- Lewy body-related pathologies process neurodegeneration hMLO model.We characterized hMLOs GBA1-/- SNCA overexpressing isogenic embryonic also body-like inclusions GBA1/SNCA dual perturbation...
Cell-to-cell propagation of α-synuclein is thought to be the underlying mechanism Parkinson's disease progression. Recent evidence suggests that inflammation plays an important role in protein aggregates. However, by which regulates aggregates remains unknown. Here, using vitro cultures, we found soluble factors secreted from activated microglia promote cell-to-cell and further showed among these factors, TNF-α had most robust stimulatory activity. Treatment neurons with triggered cellular...
Mutations in lysosomal genes increase the risk of neurodegenerative diseases, as is case for Parkinson's disease. Here, we found that pathogenic and protective mutations arylsulfatase A (ARSA), a gene responsible metachromatic leukodystrophy, storage disorder, are linked to Plasma ARSA protein levels were changed disease patients. deficiency caused increases α-synuclein aggregation secretion, propagation cells nematodes. Despite being protein, directly interacts with cytosol. The interaction...
Abstract The clinical progression of neurodegenerative diseases correlates with the spread proteinopathy in brain. current understanding mechanism is far from complete. Here, we propose that inflammation fundamental to spread. A sequence variant α-synuclein (V40G) was much less capable fibril formation than wild-type (WT-syn) and, when mixed WT-syn, interfered its fibrillation. However, V40G injected intracerebrally into mice, it induced aggregate spreading even more effectively WT-syn....
Amyloid fibril formation has been implicated in the pathogenesis of neurodegenerative diseases. Fibrillation generates numerous conformers. Presumably, conformers may possess specific biological properties, thus providing a biochemical framework for strains prions. However, precise relationship between various and their pathogenic functions not determined because limited accessibility to adequate amounts fibrils from tissue samples. α-Synuclein is one such protein, it Parkinson disease....
Parkinson's disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB) are neurodegenerative disorders alpha-synuclein (α-syn) aggregation pathology. Different strains of α-syn unique properties suggested to cause distinct clinical pathological manifestations resulting in PD, MSA, or DLB. To study individual spreading patterns, we injected fibrils amplified from brain homogenates two MSA patients PD into the brains C57BI6/J mice. Antibody staining against pS129-α-syn...
Gefitinib exerts anticancer effects on various types of cancer, such as lung, ovarian, breast, and colon cancers.However, the therapeutic gefitinib cervical cancer underlying mechanisms remain unclear.Thus, this study aimed to explore whether can be used treat elucidate mechanisms.Results showed that induced a caspase-dependent apoptosis HeLa cells, which consequently became round detached from surface culture plate.Gefitinib reorganization actin cytoskeleton downregulated expression p-FAK,...
Parkinson's disease (PD) and Multiple System Atrophy (MSA) are progressive unremitting neurological diseases that neuropathologically characterized by α-synuclein inclusions. Increasing evidence supports the aggregation of in specific brain areas early course, followed spreading pathology to multiple regions. However, little is known about how structure fibrils influence its ability seed endogenous recipient cells. Here, we aggregated seeding with homogenates PD- MSA-confirmed tissue,...
Structural variation of α-synuclein (αSyn) fibrils has been linked to the diverse etiologies synucleinopathies. However, little is known about what specific mechanism provides αSyn with pathologic features. Herein, we demonstrate Cu(II)-based supramolecular approach for unraveling formation process pathogenic and its application in a neurotoxic study. The conformation monomer was strained by macrochelation Cu(II), thereby disrupting fibril elongation while promoting nucleation. This...
Etoposide is a chemotherapeutic medication used to treat various types of cancer, including breast cancer. It established that pulsed electromagnetic field (PEMF) therapy can enhance the effects anti-cancer agents. In this study, we investigated whether PEMFs influence etoposide in MCF-7 cells and determined signal pathways affected by PEMFs. We observed co-treatment with led decrease viable compared solely treated etoposide. elevated etoposide- induced PARP cleavage caspase-7/9 activation...
Cell-to-cell propagation of protein aggregates has been implicated in the progression neurodegenerative diseases. However, underlying mechanism and modulators this process are not fully understood. Here, we screened a small-molecule library search for agents that suppress α-synuclein mutant huntingtin (mHtt). These screens yielded several molecules, some which were effective against both mHtt. Among these focused on simvastatin pravastatin. Simvastatin administration transgenic model...
Background/Aim: Gefitinib exhibits anticancer activity against cervical cancer cells via anoikis, a type of apoptosis induced by cell detachment from the extracellular matrix. Previous studies have reported that Parkin expression affects efficacy drugs. However, impact on therapeutic effects gefitinib in human remains unclear. Thus, this study aimed to evaluate whether over-expression improves HeLa cells. Materials and Methods: Cell viability apoptotic death were measured trypan blue dye...
Abstract Synucleinopathies, such as Parkinson’s disease (PD) and Multiple System Atrophy (MSA) are progressive unremitting neurological diseases. For both PD MSA, α-synuclein fibril inclusions inside brain cells neuropathological hallmarks. In addition, amplification of fibrils from body fluids is a potential biomarker distinguishing MSA. However, little known about the structure amplified human samples its connection to in brain. Here we MSA tissue, characterized seeding oligodendroglia,...
Skeletal muscle is a major regulator of glycemic control at rest, and glucose utilization increases drastically during exercise. Sustaining high via glycolysis requires efficient replenishment NAD+ in the cytosol. Apoptosis-inducing mitochondrion-associated factor 2 (AIFM2) was previously shown to be NADH oxidoreductase domain-containing flavoprotein that promotes for diet cold-induced thermogenesis. Here, we find AIFM2 selectively highly induced glycolytic extensor digitorum longus (EDL)...
Monocytes are peripheral leukocytes that function in innate immunity. Excessive triglyceride (TG) accumulation causes monocyte death and thus can compromise However, the mechanisms by which TG mediates remain unclear to date. Thus, this study aimed elucidate induces death. Results showed induced activating caspase-3/7 promoting poly (ADP-ribose) polymerase (PARP) cleavage. In addition, DNA damage activated ataxia telangiectasia mutated (ATM)/checkpoint kinase 2 ATM-and Rad3-related...
Maintaining healthy adipose tissue is crucial for metabolic health, requiring a deeper understanding of adipocyte development and response to high-calorie diets. This study highlights the importance TET3 during white (WAT) expansion. Selective depletion Tet3 in precursor cells (APCs) reduces adipogenesis, protects against diet-induced expansion, enhances whole-body metabolism. Transcriptomic analysis wild-type knockout (KO) APCs unveiled target genes, including Pparg several genes linked...
Chronic low-grade inflammation, often referred to as metainflammation, develops in response overnutrition and is a major player the regulation of insulin sensitivity. While many studies have investigated adipose tissue inflammation from perspective immune cell compartment, little known about how adipocytes intrinsically contribute metainflammation resistance at molecular level. In this study, we demonstrate novel role for Jumonji C domain-containing protein 8 (JMJD8) an adipocyte-intrinsic...