A5100757178- Parkinson's Disease Mechanisms and Treatments
- Nuclear Receptors and Signaling
- Alzheimer's disease research and treatments
- RNA regulation and disease
- CRISPR and Genetic Engineering
- Lysosomal Storage Disorders Research
- PARP inhibition in cancer therapy
- Neuroscience and Neuropharmacology Research
- Cellular transport and secretion
- Genetic Neurodegenerative Diseases
- Autophagy in Disease and Therapy
- Neurological diseases and metabolism
- Mitochondrial Function and Pathology
- Histone Deacetylase Inhibitors Research
- Nerve injury and regeneration
- Adipose Tissue and Metabolism
- Ion Channels and Receptors
- Genetics and Neurodevelopmental Disorders
- Drug Transport and Resistance Mechanisms
- Pharmacological Effects and Toxicity Studies
- Metabolism, Diabetes, and Cancer
- Biochemical Analysis and Sensing Techniques
- DNA Repair Mechanisms
- Psoriasis: Treatment and Pathogenesis
- RNA Interference and Gene Delivery
Sungkyunkwan University
2015-2025
Samsung (South Korea)
2015-2025
Samsung Medical Center
2017-2024
Pusan National University Hospital
2023
Johns Hopkins Medicine
2012-2021
Johns Hopkins University
2012-2021
Orthopaedic Research Foundation
2021
Stem Cell Institute
2011-2016
Medical Research Foundation
2016
Chosun University
2014
Mutations in PARK2/Parkin , which encodes a ubiquitin E3 ligase, cause autosomal recessive Parkinson disease (PD). Here we show that the nonreceptor tyrosine kinase c-Abl phosphorylates 143 of parkin, inhibiting parkin's ligase activity and protective function. is activated by dopaminergic stress neurotoxins, 1-methyl-4-phenylpyridinium (MPP + ) vitro vivo 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), leading to parkin inactivation, accumulation substrates aminoacyl-tRNA...
Ubiquitin mediated protein degradation is crucial for regulation of cell signaling and quality control. Poly(ADP-ribose) (PAR) a cell-signaling molecule that mediates changes in function through binding at PAR sites. Here we characterize the protein, Iduna, show it PAR-dependent ubiquitin E3 ligase. Iduna’s ligase activity requires because point mutations Y156A R157A eliminate activity. also an intact really interesting new gene (RING) domain Iduna possessing either H54A or C60A devoid...
c-Abl is activated in the brain of Parkinson's disease (PD) patients and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mice where it inhibits parkin through tyrosine phosphorylation leading to accumulation substrates neuronal cell death. In present study, we evaluated vivo efficacy nilotinib, a penetrant inhibitor, acute MPTP-induced model PD. Our results show that administration nilotinib reduces activation levels substrate, PARIS, resulting prevention dopamine (DA) neuron...
Mutations in parkin lead to early-onset autosomal recessive Parkinson's disease (PD) and inactivation of is thought contribute sporadic PD. Adult knockout the ventral midbrain mice leads an age-dependent loss dopamine neurons that dependent on accumulation interacting substrate (PARIS), zinc finger protein 746 (ZNF746), its transcriptional repression PGC-1α. Here we show adult mouse decreases mitochondrial size, number, markers consistent with a defect biogenesis. This decrease mass...
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...
Aggregation of α-synuclein contributes to the formation Lewy bodies and neurites, pathologic hallmarks Parkinson disease (PD) α-synucleinopathies. Although a number human mutations have been identified in familial PD, mechanisms that promote accumulation toxicity are poorly understood. Here, we report hyperactivity nonreceptor tyrosine kinase c-Abl critically regulates α-synuclein-induced neuropathology. In mice expressing α-synucleinopathy-associated mutation (hA53Tα-syn mice), deletion...
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...
Parkinson’s disease (PD) is a chronic progressive neurodegenerative disorder. Recent studies have implicated role for peroxisome proliferator-activated receptor γ coactivator protein-1α (PGC-1α) in PD and animal or cellular models of PD. The PGC-1α the function survival substantia nigra pars compacta (SNpc) dopamine neurons not clear. Here we find that there are four different isoforms expressed SH-SY5Y cells, these across subregions mouse brain. Adult conditional knock-out mice show...
Significance The lack of a robust transgenic mouse model loss dopamine (DA) neurons has greatly hindered the study Parkinson’s disease caused by LRRK2 mutations. In this manuscript, we report development catecholaminergic neuron-specific Tet-inducible conditional G2019S and kinase-dead mice, show that LRRK2-induced DA norepinephrine neurodegeneration is kinase-dependent can occur in cell-autonomous manner. Moreover, these models reveal α-synuclein pathology there are defects...
Mutations in PINK1 and parkin cause autosomal recessive Parkinson's disease (PD). Evidence placing common pathways regulating multiple aspects of mitochondrial quality control is burgeoning. However, compelling evidence to causatively link specific PINK1/parkin dependent dopamine neuron degeneration PD lacking. Although are known regulate mitophagy, emerging data suggest that defects mitophagy unlikely be pathological relevance. Mitochondrial functions also tied their proteasomal regulation...
Abstract Tissue expansion techniques physically expand swellable gel‐embedded biological specimens to overcome the resolution limit of light microscopy. As benefits come at expense signal concentration, imaging volume and time, mechanical integrity sample, optimal ratio may widely differ depending on experiment. However, existing methods offer only fixed ratios that cannot be easily adjusted balance gain loss associated with expansion. Here, a hydrogel conversion‐based method is presented,...
Abstract α-Synuclein misfolding and aggregation plays a major role in the pathogenesis of Parkinson’s disease. Although loss function mutations ubiquitin ligase, parkin, cause autosomal recessive disease, there is evidence that parkin inactivated sporadic Whether inactivation driver neurodegeneration disease or mere spectator unknown. Here we show through c-Abelson kinase phosphorylation three α-synuclein-induced models neurodegeneration. This results accumulation interacting substrate...
Farnesol enhances the amounts of farnesylated PARIS and PGC-1α, preventing dopaminergic neuronal loss in Parkinson’s disease models.
Pain is an unpleasant sensation experienced when tissues are damaged. Thus, pain in some way protects body from imminent threat or injury. Peripheral sensory nerves innervated to peripheral initially respond multiple forms of noxious strong stimuli, such as heat, mechanical and chemical stimuli. In response these electrical signals for conducting the nociceptive neural through axons generated. These action potentials then conveyed specific areas spinal cord brain. Sensory afferent fibers...
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)....
Nitric oxide (NO) mediates a substantial part of its physiologic functions via S-nitrosylation, however the cellular substrates for NO-mediated S-nitrosylation are largely unknown. Here we describe S-nitrosoproteome using high-density protein microarray chip containing 16,368 unique human proteins. We identified 834 potentially S-nitrosylated Using and highly specific labeling affinity capture proteins, 138 cysteine residues on 131 peptides in 95 proteins were determined, defining critical...