• BMB Reports
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• v.48 no.8
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• pp.438-444
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• 2015

Lysosomal storage diseases (LSDs) are a group of inherent diseases characterized by massive accumulation of undigested compounds in lysosomes, which is caused by genetic defects resulting in the deficiency of a lysosomal hydrolase. Currently, enzyme replacement therapy has been successfully used for treatment of 7 LSDs with 10 approved therapeutic enzymes whereas new approaches such as pharmacological chaperones and gene therapy still await evaluation in clinical trials. While therapeutic enzymes for Gaucher disease have N-glycans with terminal mannose residues for targeting to macrophages, the others require N-glycans containing mannose-6-phosphates that are recognized by mannose-6-phosphate receptors on the plasma membrane for cellular uptake and targeting to lysosomes. Due to the fact that efficient lysosomal delivery of therapeutic enzymes is essential for the clearance of accumulated compounds, the suitable glycan structure and its high content are key factors for efficient therapeutic efficacy. Therefore, glycan remodeling strategies to improve lysosomal targeting and tissue distribution have been highlighted. This review describes the glycan structures that are important for lysosomal targeting and provides information on recent glyco-engineering technologies for the development of therapeutic enzymes with improved efficacy. [BMB Reports 2015; 48(8): 438-444]

• Journal of the Korean Society of Manufacturing Process Engineers
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• v.18 no.12
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• pp.59-66
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• 2019

In this study, we developed a novel laser sintering deposition system (LSDS) based on solid free-form fabrication (SFF) technology as it has the potential to fabricate complex geometries with controllable architecture for bone tissue engineering applications. The 3D biphasic calcium phosphate (BCP) scaffolds were fabricated with a pore size of 800㎛, a line width and height of 1000㎛, and an overall size of 8.2×8.2×8.0 mm3 according to the design of experiment (DOE) results. Additionally, an optimized manufacturing process using response surface analysis was established to fabricate 3D BCP scaffolds. The fabricated 3D BCP scaffolds were sintered at 950℃, 1050℃, 1150℃, and 1250℃ according to sintering processes with a furnace. As the sintering temperature increased, the porosity increased. Through the compressive strength test, the 3D BCP scaffolds sintered at 1050℃ presented good results of about 0.76 MPa. These results suggest that fabrication methods for 3D bioceramic scaffolds using LSDS may meet the basic requirements for bone tissue engineering.

• Journal of mucopolysaccharidosis and rare diseases
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• v.2 no.1
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• pp.17-18
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• 2016

Enzyme replacement therapy (ERT) is a well-established means of treating lysosomal storage disease (LSD). However, classical IV infusion based ERT method produces less than ideal results, especially, CNS defects and quality of life in patients. To improve these main problems of parental IV formulation for LSDs, we investigate modified ERT method and evaluated the efficacy in animal model.

• BMB Reports
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• v.56 no.12
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• pp.657-662
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• 2023

Neurodegenerative diseases are characterized by distinct protein aggregates, such as those of α-synuclein and tau. Lysosomal defect is a key contributor to the accumulation and propagation of aberrant protein aggregates in these diseases. The discoveries of common proteinopathies in multiple forms of lysosomal storage diseases (LSDs) and the identification of some LSD genes as susceptible genes for those proteinopathies suggest causative links between LSDs and the proteinopathies. The present study hypothesized that defects in lysosomal genes will differentially affect the propagation of α-synuclein and tau proteins, thereby determining the progression of a specific proteinopathy. We established an imaging-based high-contents screening (HCS) system in Caenorhabditis elegans (C. elegans) model, by which the propagation of α-synuclein or tau is measured by fluorescence intensity. Using this system, we performed RNA interference (RNAi) screening to induce a wide range of lysosomal malfunction through knock down of 79 LSD genes, and to obtain the candidate genes with significant change in protein propagation. While some LSD genes commonly affected both α-synuclein and tau propagation, our study identified the distinct sets of LSD genes that differentially regulate the propagation of either α-synuclein or tau. The specificity and efficacy of these LSD genes were retained in the disease-related phenotypes, such as pharyngeal pumping behavior and life span. This study suggests that distinct lysosomal genes differentially regulate the propagation of α-synuclein and tau, and offer a steppingstone to understanding disease specificity.

• Proceedings of the Safety Management and Science Conference
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• 2011.04a
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• pp.481-486
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• 2011

The research reviews three experimental designs which include Split Plot Design (SPD), Crossover Design (CD) and Replicated Design (RD) by using Latin Square Design (LSD). SPD (CRD, LSD) and SPD (LSD, RCBD) that are derived from (S:A)${\times}B{\times}C{\times}D$ and $A{\times}B{\times}C{\times}D$. In addition, (S:A)${\times}B{\times}C$, (S:A)${\times}C{\times}D$ and (S:A)${\times}B{\times}C{\times}D$ can be used to generate various LSD and CD models. Finally, Replicated LSDs are considered to increase the power of detectability.

• Journal of Life Science
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• v.28 no.3
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• pp.351-356
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• 2018

L-Serine dehydratase (LSD) is an iron-sulfur containing enzyme that catalyzes the conversion of L-serine to pyruvate and ammonia. Among the bacterial amino acid dehydratases, it appears that only the L-serine specific enzymes utilize an iron-sulfur cluster at their catalytic site. Moreover, bacterial LSDs are classified into four types based on structural characteristics and domain arrangement. To date, only the LSD enzymes from a few bacterial strains have been studied, but more detailed investigations are required to understand the catalytic mechanism of various bacterial LSDs. In this study, LSD type II from Mycobacterium tuberculosis (MtLSD) H37Rv was expressed and purified to elucidate the biochemical and catalytic properties using the enzyme kinetic method. The L-serine saturation curve of MtLSD exhibited a typically sigmoid character, indicating an allosteric cooperativity. The values of $K_m$ and $k_{cat}$ were estimated to be $59.35{\pm}1.23mM$ and $18.12{\pm}0.20s^{-1}$, respectively. Moreover, the plot of initial velocity versus D-serine concentration at fixed L-serine concentrations showed a non-linear hyperbola decay shape and exhibited a competitive inhibition for D-serine with an apparent $K_i$ value of $30.46{\pm}5.93mM$ and with no change in the $k_{cat}$ value. These results provide insightful biochemical information regarding the catalytic properties and the substrate specificity of MtLSD.

• Journal of the Korean Society of Radiology
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• v.4 no.4
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• pp.29-32
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• 2010

The neutron capture cross section of $^{197}Au$ has been measured relative to the $^{10}B(n,{\gamma})$ standard cross section by the neutron time-of-flight(TOF) method using a 46-MeV electron linear accelerator(linac) at the Research Reactor Institute, Kyoto University(KURRI). In order to experimentally prove the result obtained, the supplementary cross section measurement has been made from 0.1 eV to 10 keV using the Kyoto University Lead slowing-down spectrometer (KULS) coupling to the linac. The relative measurement by the TOF method has been normalized to the reference value(24.5 b) at 1 eV. The evaluated capture cross sections in JENDL/D-99 Dosimetry have been compared with the current measurements by the KULS experiments.

• Proceedings of the Korean Society of Precision Engineering Conference
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• 2004.10a
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• pp.131-136
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• 2004

The limited slip differential(LSD) is a device which enables the driving force to be transmitted from one slipping wheel to another wheel in such case that the car is stuck in clay or snow. When the unwanted slipping occurs on one wheel, the LSD temporarily restraints the differential motion to transmit the driving force in the other wheel. So far, many types of LSD were developed such as mechanical lock type, disk clutch type, viscous coupling type, torsion type and multiple clutch type. However these types of LSD is too complicated and expensive, so it is used only for 4WD outdoor vehicles, military vehicles, and a portion of deluxe car. So, many studies has been devoted to improve new types of LSD to cover those demerits of existing LSDs that the hydraulic LSD is developed as arepresentative result of that. The hydraulic LSD which uses the principle of gear pump is packed with viscous oil in tight container. When a slip occurs on one wheel, the hydraulic LSD generates torque caused by high oil pressure in the container. This study has been devoted to suggest an improved hydraulic LSD. In order to achieve it, we designed a new type of hydraulic LSD, produced it and did a rig test with it on real vehicle. From the rig test, it has been confirmed that the new type of hydraulic LSD can be directly applied to exiting vehicles without changing the design criteria

• Development and Reproduction
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• v.13 no.2
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• pp.63-77
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• 2009

The neuronal ceroid-lipofuscinoses (NCLs) are a kind of neurodegenerative storage disorders. The NCLs are charecterizated by accumulation of autofluorescent lipofuscin or lipopigment in the brain. All NCL group belongs to in lysosomal storage disorders (LSDs), except Northern epilepsy. NCLs are the most common group of progressive neurodegenerative disorders in childhood, with an incidence as high as I in 12,500 live births. Four main clinical types have been described based on the onset age : infantile, late infantile, juvenile and adult types. Clinical symptoms of NCLs include loss of vision, seizures, epilepsy, progressive mental retardation and a premature death. Although mutation causes neurodegeneration in NCLs, the molecular mechanism by which mutation leads to neurodegeneration remains unclear. In this paper, we review the characteristics of these NCLs.