A5041343506- Parkinson's Disease Mechanisms and Treatments
- Nuclear Receptors and Signaling
- Lysosomal Storage Disorders Research
- Alzheimer's disease research and treatments
- RNA regulation and disease
- Neuroscience and Neuropharmacology Research
- Mitochondrial Function and Pathology
- Cellular transport and secretion
- Genetics and Neurodevelopmental Disorders
- CRISPR and Genetic Engineering
- Ion Channels and Receptors
- Genetic Neurodegenerative Diseases
- Sperm and Testicular Function
- Cardiac Fibrosis and Remodeling
- Cell Adhesion Molecules Research
- Metabolism, Diabetes, and Cancer
- Telomeres, Telomerase, and Senescence
- Bioinformatics and Genomic Networks
- PARP inhibition in cancer therapy
- Ginkgo biloba and Cashew Applications
- Advanced Biosensing Techniques and Applications
- Nerve injury and regeneration
- Pancreatic function and diabetes
- Biochemical and biochemical processes
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
Sungkyunkwan University
2015-2024
ToolGen (South Korea)
2020-2024
Samsung Medical Center
2022-2024
Samsung (South Korea)
2017-2022
Orthopaedic Research Foundation
2021
The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system has been widely used for nuclear DNA editing to generate mutations or correct specific disease alleles. Despite its flexible application, it not determined if CRISPR/Cas9, originally identified as a bacterial defense against virus, can be targeted mitochondria mtDNA editing. Here, we show that regular FLAG-Cas9 localize edit mitochondrial with sgRNAs targeting loci of the genome. Expression together gRNA Cox1...
Mutations in PTEN-induced putative kinase 1 (PINK1) and parkin cause autosomal-recessive Parkinson's disease through a common pathway involving mitochondrial quality control. Parkin inactivation leads to accumulation of the interacting substrate (PARIS, ZNF746) that plays an important role dopamine cell loss repression proliferator-activated receptor gamma coactivator-1-alpha (PGC-1α) promoter activity. Here, we show PARIS links PINK1 regulates dopaminergic neuron survival. interacts with...
Mutations in glucocerebrosidase (GBA) cause Gaucher disease (GD) and increase the risk of developing Parkinson's (PD) Dementia with Lewy Bodies (DLB). Since both genetic environmental factors contribute to pathogenesis sporadic PD, we investigated susceptibility nigrostriatal dopamine (DA) neurons L444P GBA heterozygous knock-in (GBA +/L444P ) mice 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a selective dopaminergic mitochondrial neurotoxin. We used mice, α-synuclein knockout (SNCA...
Farnesol enhances the amounts of farnesylated PARIS and PGC-1α, preventing dopaminergic neuronal loss in Parkinson’s disease models.
Progressive dopaminergic neurodegeneration is responsible for the canonical motor deficits in Parkinson's disease (PD). The widely prescribed anti-diabetic medicine metformin effective preventing animal models; however, despite significant potential of treating PD, therapeutic effects and molecular mechanisms underlying neuroprotection by are largely unknown.In this study, we found that induced substantial proteomic changes, especially metabolic mitochondrial pathways substantia nigra (SN)....
Abstract Dysfunctional parkin due to mutations or post-translational modifications contributes dopaminergic neurodegeneration in Parkinson’s disease (PD). Overexpression of provides protection against cellular stresses and prevents dopamine cell loss several PD animal models. Here we performed an unbiased high-throughput luciferase screening identify chemicals that can increase expression. Among promising inducers, hydrocortisone possessed the most favorable profiles including induction...
Abstract Transforming growth factor-β (TGF-β) acts as a key cytokine in epithelial−mesenchymal transition (EMT) and myofibroblast differentiation, which are important for normal tissue repair fibrotic diseases. Ubiquitylation proteasomal degradation of TGF-β signaling proteins regulatory mechanism the precise control signaling. SMAD-specific ubiquitin E3 ligase (SMAD ubiquitination factor 2, SMURF2) controls including receptor (TGFR) SMAD2/3. Here, we report that tetratricopeptide repeat...
Abstract The transient receptor potential vanilloid 1 (TRPV1) protein is a pain that elicits hot sensation when an organism eats the capsaicin of red chili peppers. This calcium (Ca2+)-permeable cation channel mostly expressed in peripheral nervous system sensory neurons but also central (e.g. hippocampus and cortex). Preclinical studies found TRPV1 mediates behaviors associated with anxiety depression. Loss functionality increases expression genes related to synaptic plasticity...
Aging is considered the major risk factor for neurodegenerative diseases including Parkinson’s disease (PD). Telomere shortening associated with cellular senescence. In this regard, pharmacological or genetic inhibition of telomerase activity has been used to model aging. Here, we employed CRISPR-Cas9 technology instantly remove telomere induce aging in a neuroblastoma cell line. Expression both Cas9 and guide RNA targeting repeats ablated telomere, leading retardation proliferation. Instant...
Pathological AIMP2 aggregation leads to α-synuclein inclusion and dopaminergic toxicity in Parkinson’s disease.
Abstract Vacuolar protein sorting-associated 35 (VPS35) is involved in retrograde transport of proteins from endosomes to trans-Golgi network. Gene mutations VPS35 are linked autosomal dominant late-onset Parkinson’s disease (PD). Although the identification has provided novel insight about its interactions with several PD-associated genes including leucine-rich repeat kinase 2 (LRRK2) and α -synuclein, little information available molecular mechanisms cell death downstream dysfunction. In...
RNF146 is an E3 ubiquitin ligase that specifically recognizes and polyubiquitinates poly (ADP-ribose) (PAR)-conjugated substrates for proteasomal degradation. has been shown to be neuroprotective against PAR polymerase-1 (PARP1)-induced cell death during stroke. Here we report expression inducers can prevent elicited by Parkinson's disease (PD)-associated PARP1-activating stimuli. In SH-SY5Y cells, conferred resistance toxic stimuli lead PARP1 activation. High-throughput screen using a...
Abstract Thyroid hormone (TH) has long been believed to play a minor role in male reproduction. However, evidences from experimental model of thyrotoxicosis or hypothyroidism suggests its spermatogenesis. Cellular action TH requires membrane transport via specific transporters such as monocarboxylate transporter 8 (MCT8). SLC16A2 (encodes for MCT8) inactivating mutation humans can lead Allan-Herndon Dudley-syndrome, X-linked psychomotor and growth retardation. These patients present...
The aggregation of aminoacyl transfer RNA synthetase complex-interacting multifunctional protein-2 (AIMP2) accelerates α-synuclein via direct interaction, leading to enhanced dopaminergic neurotoxicity in Parkinson's disease (PD). Thus, it would be beneficial prevent AIMP2 suppress α-synucleinopathy PD. In this study, we screened small compounds that could inhibit the vitro using a 1909 small-compound library. inhibitors (SAI-04, 06, and 08) with most effective inhibition bind AIMP2,...
The motor and nonmotor symptoms of Parkinson’s disease (PD) correlate with the formation propagation aberrant α-synuclein aggregation. This protein accumulation is a pathological hallmark disease. Our group recently showed that peucedanocoumarin III (PCIII) possesses ability to disaggregate β sheet aggregate structures, including fibrils. finding suggests PCIII could be therapeutic lead compound in PD treatment. However, translational value its safety information have never been explored...
Propagation of neuronal α-synuclein aggregate pathology to the cortex and hippocampus correlates with cognitive impairment in Parkinson's disease (PD) dementia Lewy body disease. Previously, we showed accumulation parkin substrate aminoacyl-tRNA synthetase interacting multifunctional protein-2 (AIMP2) temporal lobe postmortem brains patients advanced PD. However, potential pathological role AIMP2 dysfunction PD remains unknown.
Sangwoo Ham, Hyojung Kim, Seojin Hwang, Hyunook Kang, Seung Pil Yun, Sangjune Donghoon Hyun Sook Kwon, Yun-Song Lee, MyoungLae Cho, Heung-Mook Shin, Heejung Choi, Ka Young Chung, Han Seok Ko, Gum Hwa and Yunjong Lee. Mol. Cells 2019;42:480-94. https://doi.org/10.14348/molcells.2019.0091
The schematic diagram depicts the time schedule of intervention and analyses performed. Numerals represent days experiments were conducted. On 1th day we injected saline or MPTP (2 h interval, 4 times, 20 mg/kg free base) in 8 months WT, GBA +/L444P , SNCA−/−, SNCA−/− mice. 6th day, pole grip strength 7th mice sacrificed for indicated studies. Following are animal numbers used these studies: behavioral (n = 10), neurochemical (n = 5), immunohistochemistry biochemical studies (n = 4) per each...