• 한국동물위생학회지
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• 제44권4호
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• pp.185-194
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• 2021

Polyglutamine extension in the coding sequence of mutant huntingtin causes neuronal degeneration associated with the formation of insoluble polyglutamine aggregates in Huntington's disease (HD). Mutant huntingtin can form aggregates within the nucleus and processes of neurons possibly due to misfolding of the proteins. To better understand the mechanism by which an elongated polyglutamine causes aggregates, we have developed an in vitro binding assay system of polyglutamine tract from truncated huntingtin. We made GST-HD exon1 fusion proteins which have expanded polyglutamine epitopes (e.g., 17, 23, 32, 46, 60, 78, 81, and 94 CAG repeats). In the present emergence of new study adjusted nanotechnology on protein chip such as surface plasmon resonance strategy which used to determine the substance which protein binds in drug discovery platform is worth to understand better neurodegenerative diseases (i.e., Alzheimer disease, Parkinson disease and Huntington disease) and its pathogenesis along with development of therapeutic measures. Hence, we used strengths of surface plasmon resonance (SPR) technology which is enabled to examine binding specificity and explore targeted molecular epitope using its electron charged wave pattern in HD pathogenesis utilize conjugated mutant epitope of HD protein and its interaction whether wild type GST-HD interacts with mutant GST-HD with maximum binding affinity at pH 6.85. We found that the maximum binding affinity of GST-HD17 with GST-HD81 was higher than the binding affinities of GST-HD17 with other mutant GST-HD constructs. Furthermore, our finding illustrated that the mutant form of GST-HD60 showed a stronger binding to GST-HD23 or GST-HD17 than GST-HD60 or GST-HD81. These results indicate that the binding affinity of mutant huntingtin does not correlate with the length of polyglutamine. It suggests that the aggregation of an expanded polyglutamine might have easily occurred in the presence of wild type form of huntingtin.

• Journal of Microbiology and Biotechnology
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• 제32권9호
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• pp.1168-1177
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• 2022

Parkinson's disease (PD) is the second-most prevalent neurodegenerative disease and is characterized by dopaminergic neuronal death in the midbrain. Recently, the association between alterations in PD pathology and the gut microbiota has been explored. Microbiota-targeted interventions have been suggested as a novel therapeutic approach for PD. Agathobaculum butyriciproducens SR79^T (SR79) is an anaerobic bacterium. Previously, we showed that SR79 treatment induced cognitive improvement and reduced Alzheimer's disease pathologies in a mouse model. In this study, we hypothesized that SR79 treatment may have beneficial effects on PD pathology. To investigate the therapeutic effects of SR79 on PD, 6-hydroxydopamine (6-OHDA)-induced mouse models were used. D-Amphetamine sulfate (d-AMPH)-induced behavioral rotations and dopaminergic cell death were analyzed in unilateral 6-OHDA-lesioned mice. Treatment with SR79 significantly decreased ipsilateral rotations induced by d-AMPH. Moreover, SR79 treatment markedly activated the AKT/GSK3β signaling pathway in the striatum. In addition, SR79 treatment affected the Nrf2/ARE signaling pathway and its downstream target genes in the striatum of 6-OHDA-lesioned mice. Our findings suggest a protective role of SR79 in 6-OHDA-induced toxicity by regulating the AKT/Nrf2/ARE signaling pathway and astrocyte activation. Thus, SR79 may be a potential microbe-based intervention and therapeutic strategy for PD.

• BMB Reports
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• 제56권3호
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• pp.190-195
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• 2023

We propose a novel blood biomarker detection method that uses miRNA super-resolution imaging to enable the early diagnosis of Alzheimer's disease (AD). Here, we report a single-molecule detection method for visualizing disease-specific miRNA in tissue from an AD mice model, and peripheral blood mononuclear cells (PBMCs) from AD patients. Using optimized Magnified Analysis of Proteome (MAPs), we confirmed that five miRNAs contribute to neurodegenerative disease in the brain hippocampi of 5XFAD and wild-type mice. We also assessed PBMCs isolated from the whole blood of AD patients and a healthy control group, and subsequently analyzed those samples using miRNA super-resolution imaging. We detected more miR-200a-3p expression in the cornu ammonis 1 and dentate gyrus regions of 3 month-old 5XFAD mice than in wild-type mice. Additionally, miRNA super-resolution imaging of blood provides AD diagnosis platform for studying miRNA regulation inside cells at the single molecule level. Our results present a potential liquid biopsy method that could improve the diagnosis of early stage AD and other diseases.

• BMB Reports
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• 제56권9호
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• pp.520-525
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• 2023

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline. Several recent studies demonstrated that impaired adult neurogenesis could contribute to AD-related cognitive impairment. Adult subventricular zone (SVZ) neurogenesis, which occurs in the lateral ventricles, plays a crucial role in structural plasticity and neural circuit maintenance. Alterations in adult SVZ neurogenesis are early events in AD, and impaired adult neurogenesis is influenced by the accumulation of intracellular Aβ. Although Aβ-overexpressing transgenic 5XFAD mice are an AD animal model well representative of Aβ-related pathologies in the brain, the characterization of altered adult SVZ neurogenesis following AD progression in 5XFAD mice has not been thoroughly examined. Therefore, we validated the characterization of adult SVZ neurogenesis changes with AD progression in 2-, 4-, 8-, and 11-monthold male 5XFAD mice. We first investigated the Aβ accumulation in the SVZ using the 4G8 antibody. We observed intracellular Aβ accumulation in the SVZ of 2-month-old 5XFAD mice. In addition, 5XFAD mice exhibited significantly increased Aβ deposition in the SVZ with age. Next, we performed a histological analysis to investigate changes in various phases of adult neurogenesis, such as quiescence, proliferation, and differentiation, in SVZ. Compared to age-matched wild-type (WT) mice, quiescent neural stem cells were reduced in 5XFAD mice from 2-11 months of age. Moreover, proliferative neural stem cells were decreased in 5XFAD mice from 2 to 8 months of age. Furthermore, differentiations of neuroblasts were diminished in 5XFAD mice from 2-11 months of age. Intriguingly, we found that adult SVZ neurogenesis was reduced with aging in healthy mice. Taken together, our results revealed that impairment of adult SVZ neurogenesis appears with aging or AD progression.

• 한국식품과학회지
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• 제38권3호
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• pp.452-455
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• 2006

퇴행성뇌질환인 치매의 정확한 원인은 아직 불분명하나 빠른 뇌세포사멸이 주요한 원인으로 알려져 있다. 특히, 알츠하이머형 치매는 다량 생성되는 활성산소에 의한 뇌세포사멸이 주요원인인 것으로 입증되고 있다. 따라서 본 연구에서는 웅담활성성분인 UDCA의 세포보호 및 항산화효과로부터 알츠하이머형 치매와 같은 퇴행성 뇌질환억제 또는 치료물질로서의 가능성을 입증하고자 하였고 뇌의 대식세포인 소교세포(microglia)를 cell model로 하였다. MTT 실험결과 UDCA에 의한 세포보호효과는 $7.5\;{\mu}g/mL$ 주변 농도에서 관찰되었고 NO에 의한 세포손상 유도억제효과를 확인하였다(Fig. 2). 이와 같은 결과는 형광현미경하에서 보다 명확히 관찰되어(Fig. 3) 결국 UDCA에 의한 항세포사효과가 있음을 알 수 있었다. UDCA의 항산효과는 활성산소인 $H_2O_2$의 단백질 분해 저해능을 관찰하는 금속이온촉매 산화효과를 통해 확인하였다(Fig. 4). 즉, UDCA는 농도의존적으로$(1{\sim}100\;{\mu}g/mL)$ 단백질 분해억제능을 보였으며 $100\;{\mu}g/mL$ 이상의 농도에서 양성대조군인 ascorbic acid와 유사한 억제효과를 나타냈다. 이와 같은 UDCA의 항산화효과는 $10\;{\mu}g/mL$ 전후에서 관찰되어 세포보호효과를 나타내는 농도$(7.5\;{\mu}g/mL)$와 큰 차이가 없는 것으로 사료되었고 따라서 UDCA의 농도범주는 일괄적 적용이 가능할 것으로 판단된다. 결론적으로 웅담활성성분인 UDCA는 일반적으로 사용하여온 간질환 및 소화계질환의 보조요법제의 개념을 벗어나 항염 및 항산화효과에 잠재능을 가지며 나아가 뇌신경세포를 보호하고 세포사를 차단하여 알츠하이머와 같은 퇴행성뇌질환 조절 후보물질로 적용이 가능할 것으로 판단되나 보다 심도 있는 in vivo 및 임상적 차원의 연구가 요구된다.

• 정신신체의학
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• 제30권2호
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• pp.155-164
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• 2022

연구목적 많은 선행 연구들은 제2형 당뇨병과 알츠하이머병이나 파킨슨병과 같은 단일의 신경퇴행성 질환과의 연관성을 보고하고 있다. 본 연구는 다양한 신경퇴행성 질환을 가진 집단(ND군)과 대조군 간에 제2형 당뇨병의 발생률을 조사하여 신경퇴행성 질환과 제2형 당뇨병 발생의 연관성을 조사하고자 한다. 방 법 국민건강보험공단 맞춤형 데이터베이스 자료를 이용하여 60-84세의 노인 인구집단을 ND군과 대조군으로 분류한 뒤 이들을 후향적으로 10년간 추적관찰 하면서 제2형 당뇨병의 발생 빈도와 발생 시까지 생존시간을 평가하였다. 연구 대상자는 ND군 8,814명과 대조군 37,970명이었다. 카플란-마이어 생존 분석과 다변량 콕스 비례 위험 모형을 이용하여 생존 곡선과 위험비를 구하였다. 결 과 ND군에서 제2형 당뇨병의 발생 비율(53.6%)이 대조군(44.7%)에 비해 유의하게 높았다. ND군은 대조군과 비교하여 제2형 당뇨병의 발생 위험성이 1.4배 증가하였다(HR, 1.43; 95% CI, 1.38-1.47). 연구 대상자 중 약 1/3은 10년의 추적 기간 동안에 제2형 당뇨병이 발생하기 전에 다른 신경퇴행성 질환들이 추가로 진단되었다. 두 군 모두에서, 추적 기간 동안에 다른 신경퇴행성 질환이 추가로 진단된 경우에 그렇지 않은 경우보다 제2형 당뇨병의 발생률이 더 높았다. 결 론 ND군은 대조군에 비해 제2형 당뇨병의 발생 위험도가 약 1.4배 높았으며 신경퇴행성 질환과 제2형 당뇨병 발생은 정적인 상관관계를 보였다.

• Food Science and Biotechnology
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• 제15권5호
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• pp.735-738
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• 2006

We examined the neuroprotective and neurotrophic effects of genipin fractionated from gardenia (Gardenia jasminoides Ellis) originating from Korea. The neurotrophic effects of the genipin containing fraction was evaluated by microscopically monitoring its potency to induce neurite outgrowth in PC12h cells. The genipin containing fraction from Korean gardenia promoted neurite outgrowth in PC12h cells in this study, similar to previously reported effects by Wako Chemical, Japan. When cells were treated with the genipin containing fraction prior to ${\beta}$-amyloid peptide treatment (active domain of A peptide 25-35 treated), toxicity was significantly diminished (p<0.0l). These results suggest that genipin prepared from Korean gardenia might potentially be used as a precautionary agent in neurodegenerative disease, such as Alzheimer's disease, etc.

• 동의생리병리학회지
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• 제16권5호
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• pp.960-966
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• 2002

Ramulus et Uncus Uncariae (JGD) has sweet in flavour and slightly cold in property, acting on the liver and pericardium channels. This drug was described in a medical classic as having the ability to remove 'heat', check hyperfunction of the liver and relieve dizziness, tremors, and convulsions, and subdue 'endogenous wind'. So this study was estimated to check the anti-neuropathological effect of JGD on the Alzheimer in βAPP overexpression in neuroblastoma cell line and JGD extract was showed significantly anti-alzheimer effects (50 and 100 μg/㎖ of JGD extracts) compared with control group. Ramulus et Uncus Uncariae has anti-alzheimer effects on the βAPP overexpression in neuroblastoma cell line. So we expect that Ramulus et Uncus Uncariae may be used as a drug for neurodegenerative disease, such as stroke, Alzheimer's disease (AD). These results indicate that Ramulus et Uncus Uncariae possess strong inhibitory effect in the nervous system of apoptosis and repair effect against the degeneration of Neuroblastoma cells by βAPP expression.

• 대한한의학회지
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• 제25권4호
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• pp.188-199
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• 2004

Transglutaminase 2 (TGase 2) is an enzyme that is widely used in many biological systems for generic tissue stabilization purposes or immediate defenses for wounds. Many reports have showed that TGase 2 is aberrantly activated in tissues and cells and contributes to a variety of diseases, including neurodegenerative diseases and autoimmune diseases. In most cases, the TGase 2 appears to be a factor in the formation of inappropriate proteinaceous aggregates that may be cytotoxic. However, in other cases such as celiac disease, arthritis, lupus, amyotrophic lateral sclerosis, TGase 2 is involved in the generation of autoantibodies. This suggests the possibility that the inappropriate expression and/or presentation of TGase 2 to T cells might contribute to these diseases in genetically predisposed individuals. Others and we have found that TGase 2 expression is also increased in the inflammation process. We also demonstrated reverse of inflammation by TGase inhibition. Furthermore we discovered the genuine role of TGase 2 in immune cell activation. Increase of TGase activity induces or exacerbates inflammation via NF-κB activation without I-κBα kinase signalings. This review will examine a possibility of TGase inhibitors as therapeutic agents in a variety of inflammatory diseases.

• BMB Reports
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• 제48권4호
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• pp.200-208
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• 2015

The field of redox proteomics focuses to a large extent on analyzing cysteine oxidation in proteins under different experimental conditions and states of diseases. The identification and localization of oxidized cysteines within the cellular milieu is critical for understanding the redox regulation of proteins under physiological and pathophysiological conditions, and it will in turn provide important information that are potentially useful for the development of novel strategies in the treatment and prevention of diseases associated with oxidative stress. Antioxidant enzymes that catalyze oxidation/reduction processes are able to serve as redox biomarkers in various human diseases, and they are key regulators controlling the redox state of functional proteins. Redox regulators with antioxidant properties related to active mediators, cellular organelles, and the surrounding environments are all connected within a network and are involved in diseases related to redox imbalance including cancer, ischemia/reperfusion injury, neurodegenerative diseases, as well as normal aging. In this review, we will briefly look at the selected aspects of oxidative thiol modification in antioxidant enzymes and thiol oxidation in proteins affected by redox control of antioxidant enzymes and their relation to disease. [BMB Reports 2015; 48(4): 200-208]