• 통합자연과학논문집
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• 제13권4호
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• pp.170-180
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• 2020

Abnormal regulation, hyperphosphorylation, and aggregation of the tau protein are the hallmark of several types of dementia, including Alzheimer's Disease. Increased activity of Glycogen Synthase Kinase-3β (GSK-3β) in the Central Nervous System (CNS), increased the tau hyperphosphorylation and caused the neurofibrillary tangles (NFTs) formation in the brain cells. Over the last two decades, numerous adenosine triphosphate (ATP) competitive inhibitors have been discovered that show inhibitory activity against GSK-3β. But these compounds exhibited off-target effects which motivated researchers to find new GSK-3β inhibitors. In the present study, we have collected the dataset of 31 C-Glycosylflavones derivatives that showed inhibitory activity against GSK-3β. Among the dataset, the most active compound was docked with the GSK-3β and molecular dynamics (MD) simulation was performed for 50 ns. Based on the 50 ns MD pose of the most active compound, the other dataset compounds were sketched, minimized, and aligned. The 3D-QSAR based Comparative Molecular Field Analysis (CoMFA) model was developed, which showed a reasonable value of q2=0.664 and r2=0.920. The contour maps generated based on the CoMFA model elaborated on the favorable substitutions at the R2 position. This study could assist in the future development of new GSK-3β inhibitors.

• 대한영상의학회지
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• 제83권3호
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• pp.453-472
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• 2022

양전자방출단층촬영(PET)을 이용한 단백질병리의 생체영상기술은 퇴행성 치매의 질병 기전을 이해하는데 필요한 정보를 제공할 뿐 아니라, 질병의 조기 발견과 치료법 개발에서 중요한 역할을 수행하고 있다. 베타아밀로이드와 타우 PET 영상은 인체 뇌병리에 기반한 알츠하이머병 연속체에 대한 진단 바이오마커로 확립되어 조기진단과 감별진단을 용이하게 하고, 질병 예후를 예측하고 있다. 또한, 치매치료제 개발에서 예후 및 대리 바이오마커로의 역할이 커지고 있다. 이 종설에서는 치매를 유발하는 알츠하이머병 및 기타 퇴행성 뇌질환에서 베타아밀로이드와 타우 단백질의 뇌축적을 영상화하는 PET의 최근 임상적 적용과 최근 동향을 살펴보고, 잠재적 유용성을 소개하고자 한다.

• 한방재활의학과학회지
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• 제25권1호
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• pp.1-15
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• 2015

Objectives The aim of this study was to investigate the effects of Cannabis Fructus on exercise capacity and cognitive function in chronic hypoperfusion induced vascular dementia rat model. Methods Vascular dementia rat models were induced by chronic cerebral hypoperfusion through bilateral common carotid arteries occlusion (BCCAO). All rats were randomly divided into 4 groups: normal group; control group; CF I group (feeding Cannabis Fructus 100 mg/kg); CF II group (feeding Cannabis Fructus 300 mg/kg). In order to study the effects of oral administration of Cannabis Fructus on vascular dementia rat models, corner turn test, hole board test, radial arm maze test, passive avoidance test were taken and Acetylcholine (ACh) activity, Acetylcholinesterase (AChE) activity, serum of Vascular endothelial growth factor (VEGF) protein level were measured. Also histological findings of the liver, kidney, brain and the change of Tau immunoreactive neurons in hippocampus were observed. Results CF I and CF II showed significant improvement in corner turn test, hole board test, radial arm maze test, passive avoidance test, Acetylcholine (ACh) activity, Acetylcholinesterase (AChE) activity, the serum of Vascular endothelial growth factor (VEGF) protein level and the change of Tau immunoreactive neurons in hippocampus. CF I showed more significant effect than CF II in these tests. However in histological observations of the liver and kidney both CF I and CF II showed glomerular injury and hepatotoxicity. Conclusions These results suggest that Cannabis Fructus was helpful in improving exercise capacity and cognitive function on Chronic hypoperfusion induced Vascular Dementia rats. However Cannabis Fructus affects the liver and kidney, therefore suggest that this is an area for further study.

• 대한간호학회지
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• 제53권4호
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• pp.371-384
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• 2023

Purpose: With an increase in the aging population, the number of patients with degenerative spinal diseases undergoing surgery has risen, as has the incidence of postoperative delirium. This study aimed to investigate the risk factors affecting postoperative delirium in older adults who had undergone spine surgery and to identify the associated biomarkers. Methods: This study is a prospective study. Data of 100 patients aged ≥ 70 years who underwent spinal surgery were analyzed. Demographic data, medical history, clinical characteristics, cognitive function, depression symptoms, functional status, frailty, and nutritional status were investigated to identify the risk factors for delirium. The Confusion Assessment Method, Delirium Rating Scale-R-98, and Nursing Delirium Scale were also used for diagnosing delirium. To discover the biomarkers, urine extracellular vesicles (EVs) were analyzed for tau, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), neurofilament light, and glial fibrillary acidic protein using digital immunoassay technology. Results: Nine patients were excluded, and data obtained from the remaining 91 were analyzed. Among them, 18 (19.8%) developed delirium. Differences were observed between participants with and without delirium in the contexts of a history of mental disorder and use of benzodiazepines (p = .005 and p = .026, respectively). Tau and UCH-L1-concentrations of urine EVs-were comparatively higher in participants with severe delirium than that in participants without delirium (p = .002 and p = .001, respectively). Conclusion: These findings can assist clinicians in accurately identifying the risk factors before surgery, classifying high-risk patients, and predicting and detecting delirium in older patients. Moreover, urine EV analysis revealed that postoperative delirium following spinal surgery is most likely associated with brain damage.

• Mass Spectrometry Letters
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• 제9권1호
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• pp.17-23
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• 2018

Studies on the interactions of amyloidogenic proteins with trace metals, such as copper, have indicated that the metal ions perform a critical function in the early oligomerization process. Herein, we investigate the effects of Cu(II) ions on the active sequence regions of amyloidogenic proteins using electrospray ionization mass spectrometry (ESI-MS) and collision induced dissociation tandem MS (CID-MS/MS). We chose three amyloidogenic peptides NNQQNY, LYQLEN, and VQIVYK from yeast prion like protein Sup35, insulin chain A, and tau protein, respectively. [Cu-peptide] complexes for all three peptides were observed in the mass spectra. The mass spectra also show that increasing Cu(II) concentrations decrease the population of existing peptide oligomers. The tandem mass spectrum of NNQQNY shows preferential binding for the N-terminal region. All three peptides are likely to appear to be in a Cu-monomer-monomer (Cu-M-M) structure instead of a monomer-Cu-monomer (M-Cu-M) structure.

• Mass Spectrometry Letters
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• 제10권1호
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• pp.32-37
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• 2019

The ${\pi}-{\pi}$ interactions of the peptide-dimer and peptide-trimer complexes were investigated in the (VQIVYK + LYQLEN) and (VQIVYK + NNQQNY) mixing solutions. The results showed that tyrosine (Y) residues were critical in the formation of hetero peptide-dimers and -trimers during the early oligomerization process. We used collision-induced dissociation (CID) along with electrospray ionization mass spectroscopy (ESI-MS) to obtain the structural information of the hetero-dimers and -trimers. We chose three amyloidogenic peptides-VQIVYK, NNQQNY, and LYQLEN-from tau protein, yeast prion-like protein Sup35, and insulin chain A, respectively. Hetero-dimer, -trimer, -tetramer, and -pentamer complexes were observed in the mass spectra. The tandem mass spectrum of the hetero-dimer and hetero-trimer showed two different fragmentation patterns (covalent and non-covalent bond dissociation). Y-Y interaction structures were also proposed for the hetero-dimer and -trimer complexes.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.208.1-208.1
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• 2003

In recent, growing aged people in coupled with the increased senile dementia, Alzheimer's disease, has been a social interests to be cleared out. Alzheimer Disease(AD), first reported by Alios Alzheimer (1864-1915) in 1907, is a neurodegenrative disease. Nothing exact cause of AD is available by now, but in clinical founding ${\beta}$-amyloid peptide(A${\beta}$) and microtubule associated protein($\tau$ protein) is to involved in the disease, and the most important feature in AD is Known to induce chronic inflammation to neuron cell. (omitted)

• 생명과학회지
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• 제23권9호
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• pp.1096-1103
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• 2013

만성외상성뇌병증(Chronic traumatic encephalopathy, CTE)은 운동선수와 매우 밀접하게 관련되어 있으며 장기간에 걸쳐 반복적인 외상성뇌손상(traumatic brain injury, TBI)로 인한 퇴행성뇌질환이다. 신경영양인자(neurotrophic factor)는 여러 종류가 알려져 있으며 이들은 뇌와 척수의 물리적 손상시에 신경보호효과가 있다. 따라서, 신경영양인자의 혼합물인 cebrolysin을 이용하여 CTE질환에 가장 적합하다고 여겨지는 repetitive mild TBI (rmTBI) 모델에서 cerebrolysin의 신경보호효과를 알아보고자 하였다. 실험군은 5군(groups 1 and 2: rmTBI for 4 weeks following cerebrolysin injection for 4 weeks; groups 3 and 4: rmTBI for 8 weeks with or without cerebrolysin injection for 4 weeks; group 5: control)으로 나누어 진행하였다. CTE의 가장 대표적 표시인자인 tau 단백질의 인산화를 조직학적으로 조사한 결과, 대뇌겉질과 해마내 CA3 영역에서 phospho-tau단백질의 발현이 증가되었으며 cerebrolysin ($10{\mu}l$ of 1 mg/ml)를 미정맥으로 투여시 p-tau발현이 감소되었다. CTE의 병인으로 알려진 별아교세포와 미세아교세포의 활성을 각각의 표시인인 GFAP, iba-1을 이용하여 면역조직화학염색을 시행하였다. 별아교세포의 활성은 rmTBI에 의하여 증가하였으며 cerebrolysin에 의해 회복되었으나 미세아교세포의 활성은 관찰되지 않았다. 또한 rmTBI모델에서 체내 탐식세포(macrophage)의 뇌내유입유무를 관찰하고자 CD45 염색을 시행하였으나 유의한 차이를 관찰하지 못하였다. 이상의 결과를 종합하면, cerebrolysin이 rmTBI에 의한 tau단백질의 인산화 및 별아교세포의 활성을 조절하는 것으로 사료된다. 따라서 cerebrolysin이 CTE 환자에 대한 치료 약물의 후보가 될 수 있음을 시사한다.

• Biotechnology and Bioprocess Engineering:BBE
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• 제10권3호
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• pp.284-288
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• 2005

Baker's yeast was disrupted in a 1.4-L stainless steel horizontal bead mill under a continuous recycle mode using 0.3 mm diameter zirconia beads as abrasive. A single pass in continuous mode bead mill operation liberates half of the maximally released protein. The maximum total protein release can only be achieved after passaging the cells 5 times through the disruption chamber. The degree of cell disruption was increased with the increase in feeding rate, but the total protein release was highest at the middle range of feeding rate (45 L/h). The total protein release was increased with an increase in biomass concentration from 10 to $50\%$(w/v). However, higher heat dissipation as a result of high viscosity of concentrated biomass led to the denaturation of labile protein such as glucose 6-phosphate dehydrogenase (G6PDH). As a result the highest specific activity of G6PDH was achieved at biomass concentration of $20\%$(ww/v). Generally, the degree of cell disruption and total protein released were increased with an increase in impeller tip speed, but the specific activity of G6PDH was decreased substantially at higher impeller tip speed (14 m/s). Both the degree of cell disruption and total protein release increased, as the bead loading increased from 75 to $85\% (v/v)$. Hence, in order to obtain a higher yield of labile protein such as G6PDH, the yeast cell should not be disrupted at biomass concentration and impeller tip speed higher than $20\%(w/v)$ and 10 m/s, respectively.

• Animal cells and systems
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• 제9권3호
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• pp.161-171
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• 2005

Integrin-linked kinase 1 (ILK1) regulates several protein kinases, including PKB/Akt kinase and glycogen synthase kinase ${\beta}$. ILK1 is also involved distinctively in the cell morphological and structural functions by interacting with the components of the extracellular matrix or integrin. According to the information of serum- and glucocorticoid-induced kinase 1 (SGK1) substrate specificity (R-X-R-X-X(S/T)-${\phi};{\phi}$ indicates a hydrophobic amino acid), two putative phosphorylation sites, $Thr^{181}\;and\;Ser^{246}$, were found in ILK1. We showed that ILK1 fusion protein and two fluorescein-labeled ILK1 peptides, $FITC-^{174}RTRPRNGTLN^{183}$ and $FITC-^{239}CPRLRIFSHP^{248}$, were phosphorylated by SGK1 in vitro. We also identified that 14-3-3 ${\theta}\;{\varepsilon}\;and\;{\xi}$, among several 143-3 isotypes $({\beta},\;{\gamma},\;{\varepsilon},\;{\eta},\;{\sigma},\;{\theta},\;{\tau}\;and\;{\xi})$ formed protein complex with ILK1 in COS-1 cells. Furthermore, the phosphorylation of $Ser^{246}$ by SGK1 induced the binding with 14-3-3. It was also demonstrated that 14-3-3-bound ILK1 has reduced kinase activity. Thus, these data suggest that SGK1 phosphorylates $Thr^{181}\;and\;Ser^{246}$ of ILK1 and the phosphorylation of its $Ser^{246}$ makes ILK1 bind to 14-3-3, resulting in the inhibition of ILK1 kinase activity.