• Journal of Korean Neurosurgical Society
• /
• 제63권5호
• /
• pp.579-589
• /
• 2020

Objective : No optimum genetic rat Huntington model both neuropathological using an adeno-associated virus (AAV-2) vector vector has been reported to date. We investigated whether direct infection of an AAV2 encoding a fragment of mutant huntingtin (AV2-82Q) into the rat striatum was useful for optimizing the Huntington rat model. Methods : We prepared ten unilateral models by injecting AAV2-82Q into the right striatum, as well as ten bilateral models. In each group, five rats were assigned to either the 2×10¹² genome copies (GC)/mL of AAV2-82Q (×1, low dose) or 2×10¹³ GC/mL of AAV2-82Q (×10, high dose) injection model. Ten unilateral and ten bilateral models injected with AAV-empty were also prepared as control groups. We performed cylinder and stepping tests 2, 4, 6, and 8 weeks after injection, tested EM48 positive mutant huntingtin aggregates. Results : The high dose of unilateral and bilateral AAV2-82Q model showed a greater decrease in performance on the stepping and cylinder tests. We also observed more prominent EM48-positive mutant huntingtin aggregates in the medium spiny neurons of the high dose of AAV2-82Q injected group. Conclusion : Based on the results from the present study, high dose of AAV2-82Q is the optimum titer for establishing a Huntington rat model. Delivery of high dose of human AAV2-82Q resulted in the manifestation of Huntington behaviors and optimum expression of the huntingtin protein in vivo.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
• /
• pp.65-66
• /
• 2003

The cause of Huntington's disease (HD) is a pathological expansion of the polyglutamine domain within the N-terminal region of huntingtin. Neuronal aggregates composed of mutant huntingtin within certain neuronal populations are a characteristic hallmark of HD. Because tissue transglutaminase (tTG) cross-links proteins into aggregates and polypeptide-bound glutamines are primary determining factors for tTG-catalyzed reactions, it has been hypothesized that tTG may contribute to the formation of aggregates. (omitted)

• BMB Reports
• /
• 제56권3호
• /
• pp.178-183
• /
• 2023

Huntington's disease (HD) is a neurodegenerative disorder, of which pathogenesis is caused by a polyglutamine expansion in the amino-terminus of huntingtin gene that resulted in the aggregation of mutant HTT proteins. HD is characterized by progressive motor dysfunction, cognitive impairment and neuropsychiatric disturbances. Histone deacetylase 6 (HDAC6), a microtubule-associated deacetylase, has been shown to induce transport- and release-defect phenotypes in HD models, whilst treatment with HDAC6 inhibitors ameliorates the phenotypic effects of HD by increasing the levels of α-tubulin acetylation, as well as decreasing the accumulation of mutant huntingtin (mHTT) aggregates, suggesting HDAC6 inhibitor as a HD therapeutics. In this study, we employed in vitro neural stem cell (NSC) model and in vivo YAC128 transgenic (TG) mouse model of HD to test the effect of a novel HDAC6 selective inhibitor, CKD-504, developed by Chong Kun Dang (CKD Pharmaceutical Corp., Korea). We found that treatment of CKD-504 increased tubulin acetylation, microtubule stabilization, axonal transport, and the decrease of mutant huntingtin protein in vitro. From in vivo study, we observed CKD-504 improved the pathology of Huntington's disease: alleviated behavioral deficits, increased axonal transport and number of neurons, restored synaptic function in corticostriatal (CS) circuit, reduced mHTT accumulation, inflammation and tau hyperphosphorylation in YAC128 TG mouse model. These novel results highlight CKD-504 as a potential therapeutic strategy in HD.

• 한국독성학회:학술대회논문집
• /
• 한국독성학회 1998년도 국제심포지움 및 추계학술대회
• /
• pp.37-41
• /
• 1998

• 대한약리학회:학술대회논문집
• /
• 대한약리학회 2006년도 The 6th Congress of the Federation of Asian and Oceanian Physiological Societies
• /
• pp.107.2-107.2
• /
• 2006

• 한국수학교육학회지시리즈A:수학교육
• /
• 제28권1호
• /
• pp.57-61
• /
• 1989

• 한국자기공명학회논문지
• /
• 제24권2호
• /
• pp.43-46
• /
• 2020

Huntington's disease (HD) is an inherited neurodegenerative disease caused by abnormal polyglutamine (polyQ) expansion in the huntingtin protein (Htt). There is no cure for HD so far. Although exact molecular mechanism of HD pathogenesis is still elusive, fibril formation of the expanded Htt is linked to the toxicity. In this study, we prepared the expanded Htt containing 46 glutamines, and induced the fibrillation by proteolytic cleavage. Fibrillation of the pathogenic Htt has been monitored by time course NMR experiment. The NMR-based monitoring method could be widely used to screen the candidates to inhibit the fibrillation of the pathogenic Htt.

• Journal of Korean Society for Atmospheric Environment
• /
• 제9권E호
• /
• pp.397-400
• /
• 1993

The possible air pollution problems in a proposed underground highway are discussed using carbon monoxide (CO) as an indicator. Carbon monoxide concentrations in the underground highway depend on several factors, including the size of tunnel, the number of automobiles, the CO emission rate, and the tunnel ventilation rate. Using the estimated values, CO concentrations in the underground highway can be predicted. Without proper ventilation system, CO concentration in the underground highway can be dangerous level. However, the cost of operating the mandatory mechanical ventilation system may be tremendouslyy high and may be technically unrealistic to implement. If the underground highway is constructed with proper ventilation system, a continuous air pollution monitoring system with alarming function must be installed to alert personnel of serious air pollution built up in the underground highway. Traffic must be restricted, whenever the inside air pollution levels exceed agreed values. Short distances between evacuation exits are necessary for emergency situations or malfunction of ventilation system.

• 대한핵의학회지
• /
• 제37권1호
• /
• pp.13-23
• /
• 2003

Neurodegenerative disorders cause a variety of dementia including Alzheimer disease, frontotemporal dementia, dementia with Lewy bodies, corticobasal degeneration, progressive supranuclear palsy, and Huntington's disease. PET scan is useful for early detection and differential diagnosis of these dementing disorders. Also, it provides valuable information about clinico-anatomical correlation, allowing better understanding of function of brain. Here we discuss recent achievements PET studies regarding these dementing disorders. Future progress in PET technology, new tracers, and image analysis will play an important role in further clarifying the disease pathophysiology and brain functions.

• 한국동물번식학회:학술대회논문집
• /
• 한국동물번식학회 2003년도 학술발표대회 발표논문초록집
• /
• pp.80-80
• /
• 2003

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms, accompanied by marked cell death in the striatum and cortex. Stereotaxic injection of quinolinic acid (QA) into striatum results in a degeneration of GABAergic neurons and exhibits abnormal motor behaviors typical of the illness. The objective of this study was carried out to obtain basic information about whether parthenogenetic mouse embryonic stem (PmES) cells are suitable for cell replacement therapy of HD. To establish PmES cell lines, hybrid F1 (C57BL/6xCBA/N) mouse oocytes were treated with 7% ethanol for 5 min and cytochalasin-B for 4 hr to initiate spontaneous cleavage. Thus established PmES cells were induced to differentiate using bFGF (20ng/ml) followed by selection of neuronal precursor cells for 8 days in N2 medium. After selection, cells were expanded at the presence of bFGF (20 ng/ml) for another 6 days, then a final differentiation step in N2 medium for 7 days. To establish recipient animal models of HD, young adult mice (7 weeks age ICR mice) were lesioned unilaterally with a stereotaxic injection of QA (60 nM) into the striatum and the rotational behavior of the animals was tested using apomorphine (0.1mg/kg, IP) 7 days after the induction of lesion. Animals rotating more than 120 turns per hour were selected and the differentiated PmES cells (1$\times$10$^4$cells/ul) were implanted into striatum. Four weeks after the graft, immunohistochemical studies revealed the presence of cells reactive to anti-NeuN antibody. However, only a slight improvement of motor behavior was observed. By Nissl staining, cell mass resembling tumor was found at the graft site and near cortex which may explain the slight behavioral improvement. Detailed experiment on cell viability, differentiation and migration explanted in vivo is currently being studied.