• 생명과학회지
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• 제29권6호
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• pp.740-746
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• 2019

운동은 치매에 긍정적인 영향을 줄 수 있다고 잘 알려져 있다. 그러나 대부분의 치매 관련 연구에서는 치매의 증상 완화, 치매에 관한 다양한 치료 및 약물 치료에 대한 연구가 대부분이었다. 규칙적인 운동은 뇌 기능과 치매예방에 중요한 역할을 하지만, 치매와 뇌 기능에 대한 운동의 효과를 나타내는 연구는 부족한 실정이다. 본 연구에서는 운동이 수면 관련 인자(melatonin, serotonin), 치매 관련 인자(BDNF, beta-amyloid, IGF-1, Irisin, GLUT)에 미치는 영향에 대해 연구하고자 한다. 본 연구는 Myokine (Irisin, IGF-1), GLUT 및 Melatonin이 지구성 운동을 통한 BDNF 활성화를 통해 치매 증상을 개선하거나 지연시키는 중요한 인자라는 것을 밝혀냈다. 그러나 이러한 결과는 다양한 종류의 운동 유형, 형태, 기간 및 운동 강도 등에 따라 다른 결과가 나타나서 논란의 여지가 있다. 그러므로 추후 운동과 치매에 관한 기전적인 연구분석이 필요하다.

• 한국자기공명학회논문지
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• 제15권2호
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• pp.175-186
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• 2011

Amyloid fibrils have long been known to be the well known ${\alpha}$-helix to ${\beta}$-sheet transition characterizing the conversion of cellular to scrapie forms of the prion protein. A very short sequence of Yeast prion-like protein, GNNQQNY (SupN), is responsible for aggregation that induces diseases. KSI-fused tandem repeats of SupN vector are constructed and used to express SupN peptide in Escherichia coli (E.Coli). A method for a production, purification, and cleavage of tandem repeats of recombinant isotopically enriched SupN in E. coli is described. This method yields as much as 20 mg/L of isotope-enriched fusion proteins in minimal media. Synthetic SupN peptides and $^{13}C$ Gly labeled SupN peptides are studied by Congo Red staining, Birefringence and transmission electron microscopy to characterize amyloid fibril formation. To get a better understanding of aggregation-structure relationship of 7 residues of Yeast prion-like protein, the change of a conformational structure will be studied by $^{13}C$ solid-state nmr spectroscopy as powder of both amorphous and fibrillar forms.

• Bulletin of the Korean Chemical Society
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• 제35권12호
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• pp.3542-3546
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• 2014

Relationship between molecular freedom of amyloidogenic protein and its self-assembly into amyloid fibrils has been evaluated with ${\alpha}$-synuclein, an intrinsically unfolded protein related to Parkinson's disease, by restricting its structural plasticity through an end-to-end disulfide bond formation between two newly introduced cysteine residues on the N- and C-termini. Although the resulting circular form of ${\alpha}$-synuclein exhibited an impaired fibrillation propensity, the restriction did not completely block the protein's interactive core since co-incubation with wild-type ${\alpha}$-synuclein dramatically facilitated the fibrillation by producing distinctive forms of amyloid fibrils. The suppressed fibrillation propensity was instantly restored as the structural restriction was unleashed with ${\beta}$-mercaptoethanol. Conformational flexibility of the accreting amyloidogenic protein to pre-existing seeds has been demonstrated to be critical for fibrillar extension process by exerting structural adjustment to a complementary structure for the assembly.

• 한국임상수의학회지
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• 제40권6호
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• pp.408-413
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• 2023

The incidence of canine cognitive dysfunction syndrome (CCDS), a prominent geriatric disease, is increasing because of the extended lifespan of companion animals. Various complementary therapies have been proposed for the management of CCDS. This study evaluated the clinical efficacy of the Brain Six Complex Extract^ⓒ in dogs with cognitive dysfunction syndrome (CDS). Fifteen dogs with CDS were included, and four to five drops of Brain Six Complex Extract^ⓒ, composed of herbal extracts, were applied around the dorsal neck of all dogs twice daily for 1-3 months. Clinical efficacy was evaluated using the CCDS scale, and serum β-amyloid oligomer concentrations were measured before and after administration of the extract. The CCDS scale score significantly decreased after administration in dogs with CDS (p = 0.0313), compared to pre-administration levels. Although the serum β-amyloid oligomer concentration decreased after administration, the change was not statistically significant (p > 0.05). A notable decrease was observed between pre- and post-administration in dogs with β-amyloid levels >300 pg/mL (p = 0.0313). The laboratory results showed no remarkable adverse effects of the extract. This study suggests that Brain Six Complex Extract^ⓒ extract could be an adjunctive treatment for dogs with CDS.

• Biomolecules & Therapeutics
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• 제19권3호
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• pp.288-295
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• 2011

Amyloid beta ($A{\beta}$)-induced neurotoxicity is a major pathological mechanism of Alzheimer's disease (AD). In this study, we investigated the inhibitory effect of L-theanine, a component of green tea (Camellia sinensis) on $A{\beta}_{1-42}$-induced neurotoxicity and oxidative damages of macromolecules. L-theanine inhibited $A{\beta}_{1-42}$-induced generation of reactive oxygen species, and activation of extracellular signal-regulated kinase and p38 mitogenic activated protein kinase as well as the activity of nuclear factor kappa-B. L-theanine also signifi cantly reduced oxidative protein and lipid damage, and elevated glutathione level. Consistent with the reduced neurotoxic signals, L-theanine (10-50 ${\mu}g$/ml) concomitantly attenuated $A{\beta}_{1-42}$ (5 ${\mu}M$)-induced neurotoxicity in SK-N-MC and SK-N-SH human neuroblastoma cells. These data indicate that L-theanine on $A{\beta}$-induced neurotoxicity prevented oxidative damages of neuronal cells, and may be useful in the prevention and treatment of neurodegenerative disease like AD.

• 동의신경정신과학회지
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• 제17권2호
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• pp.75-89
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• 2006

Objective : This experiment was designed to investigate the effect of Rhododendron simsii Planch(RSP) on the Alzheimer's disease. Method : The effects of RSP on amyloid precursor proteins(APP), acetylcholinesterase (AChE), glial fibrillary acidic protein(GFAP) mRNA of PC-12 cell treated by amyloid ${\beta}$ protein$(A{\beta})$ and $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ mRNA of THP-1 cell treated by lipopolysaccharide(LPS), AChE activity of PC-12 cell lysate treated by $A{\beta}$ and behavior of the memory deficit mice induced by scopolamine, and glucose, AChE in serum of the memory deficit mice induced by scopolamine were investigated, respectively. Result : 1. RSP suppressed APP, AChE, GFAP mRNA in PC-12 celt treated by $A{\beta}$. 2. RSP suppressed $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ mRNA in THP-1 cell treated by LPS. 3. RSP suppressed AChE activity in cell lysate of PC-12 cell treated by $A{\beta}$. 4. RSP increased glucose and decreased AChE significantly in the serum of the memory deficit mice induced by scopolamine. 5. RSP group showed significantly inhibitory effect on the scopolamine-induced impairment of teaming and. memory in the experiment of Morris water maze. Conclusion : According to the above results, it is suggested that RSP might be usefully applied for prevention and treatment of Alzheimer's disease and memory deficit symptom.

• The Korean Journal of Physiology and Pharmacology
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• 제17권3호
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• pp.189-195
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• 2013

Amyloid-${\beta}$ peptide ($A{\beta}$), generated by proteolytic cleavage of the amyloid precursor protein (APP), plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). The key step in the generation of $A{\beta}$ is cleavage of APP by beta-site APP-cleaving enzyme 1 (BACE1). Levels of BACE1 are increased in vulnerable regions of the AD brain, but the underlying mechanism is unknown. In the present study, we reported the effects of ferrous ions at subtoxic concentrations on the mRNA levels of BACE1 and a-disintegrin-and-metalloproteinase 10 (ADAM10) in PC12 cells and the cell responses to ferrous ions. The cell survival in PC12 cells significantly decreased with 0 to 0.3 mM $FeCl_2$, with 0.6 mM $FeCl_2$ treatment resulting in significant reductions by about 75%. 4,6-diamidino-2-phenylindole (DAPI) staining showed that the nuclei appeared fragmented in 0.2 and 0.3 mM $FeCl_2$. APP-${\alpha}$-carboxyl terminal fragment (APP-${\alpha}$-CTF) associations with ADAM10 and APP-${\beta}$-CTF with BACE1 were increased. Levels of ADAM10 and BACE1 mRNA increased in response to the concentrations of 0.25 mM, respectively. In addition, p-ERK and p-Bad (S112, S155) expressions were increased, suggesting that APP-CTF formation is related to ADAM10/ BACE1 expression. Levels of Bcl-2 protein were increased, but significant changes were not observed in the expression of Bax. These data suggest that ion-induced enhanced expression of AMDA10/BACE1 could be one of the causes for APP-${\alpha}/{\beta}$-CTF activation.

• Nutrition Research and Practice
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• 제9권5호
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• pp.480-488
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• 2015

BACKGROUND/OBJECTIVES: Alzheimer's disease (AD) is characterized by deficits in memory and cognitive functions. The accumulation of amyloid beta peptide ($A{\beta}$) and oxidative stress in the brain are the most common causes of AD. MATERIALS/METHODS: Caffeic acid (CA) is an active phenolic compound that has a variety of pharmacological actions. We studied the protective abilities of CA in an $A{\beta}_{25-35}$-injected AD mouse model. CA was administered at an oral dose of 10 or 50 mg/kg/day for 2 weeks. Behavioral tests including T-maze, object recognition, and Morris water maze were carried out to assess cognitive abilities. In addition, lipid peroxidation and nitric oxide (NO) production in the brain were measured to investigate the protective effect of CA in oxidative stress. RESULTS: In the T-maze and object recognition tests, novel route awareness and novel object recognition were improved by oral administration of CA compared with the $A{\beta}_{25-35}$-injected control group. These results indicate that administration of CA improved spatial cognitive and memory functions. The Morris water maze test showed that memory function was enhanced by administration of CA. In addition, CA inhibited lipid peroxidation and NO formation in the liver, kidney, and brain compared with the $A{\beta}_{25-35}$-injected control group. In particular, CA 50 mg/kg/day showed the stronger protective effect from cognitive impairment than CA 10 mg/kg/day. CONCLUSIONS: The present results suggest that CA improves $A{\beta}_{25-35}$-induced memory deficits and cognitive impairment through inhibition of lipid peroxidation and NO production.

• The Journal of Korean Physical Therapy
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• 제33권3호
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• pp.136-141
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• 2021

Purpose: Dementia is a disease in which cognitive function declines, leading to deterioration of body functions and activities of daily living. The purpose of this study is to explore the effects of dual-task training, including cognitive tasks, on cognitive and body function and β-amyloid levels in Alzheimer's dementia patients. Methods: 34 inpatients diagnosed with Alzheimer's dementia at a nursing hospital located in South Korea. The patients were randomly divided into a dual-task group (n=16) and a single-task group (n=18). Each group was trained for 30 minutes three times a week for eight weeks. The MMSE-K was used to measure the patients' cognitive function. To assess the patients' static balance ability, their LOS was measured using BioRescue. while dynamic balance was measured using the BBS. The 10MWT were conducted to evaluate the patients' walking ability. Blood analysis was performed to measure levels of β-amyloid. Results: Both groups exhibited statistically significant improvements in gait function after the training (p<0.05). The dual-task group exhibited statistically significant differences in cognitive function, static and dynamic balance function, and β-amyloid levels after training (p<0.05). A significant difference was observed between the two groups (p<0.05). Conclusion: Dual-task training were found to be effective in improving cognitive and bodily functioning and reducing β-amyloid levels in Alzheimer's dementia patients. Thus, this may be suggested as an effective exercise method for the treatment and early prevention of Alzheimer's dementia.

• 동의신경정신과학회지
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• 제21권2호
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• pp.125-140
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• 2010

Objectives : The purpose of this study is to examine from various angles the protective effect of Gastrodia elata Blume (GEB) against nerve cell death induced by $\beta$-amyloid by using the cell line SH-SY5Y, which is commonly utilized for toxicity testing in nerve cells, and to find out its mechanism of action. Methods : To begin with, as a result of assessing the rate of cell survival by employing MTT reduction assay, the treatment with $\beta$-amyloid at different concentrations caused cytotoxicity, which was inhibited by preprocessing GEB extract. In addition, after $\beta$-amyloid was processed with the cell SH-SY5Y, apoptosis progressed, which was reduced effectively by processing GEB extract. Results : When cytotoxicity was caused by using hydrogen peroxide, a representative ROS, in order to examine the antioxidant effect of GEB, its protective effect was also observed. Apart from ROS, reactive nitrogen species (RNS) are also known to play a crucial role in nerve cell death. The treatment with the NO donor SNAP increased the production of nitric oxide and the expression of iNOS, which was also inhibited by GEB extract. Meanwhile, as an attempt to find out the mechanism of action explaining the antioxidant effect, the intracellular antioxidant enzyme expressions were measured by RT-PCR, which showed that GEB extract increased the expressions of heme oxygenase-1, GAPDH and $\gamma$-glutamate cysteine ligase. Lastly, GEB extract had a protective effect against impaired memory induced by scopolamine in animal models (in vivo). Conclusions : These findings indicate that GEB has a protective effect against the death of cranial nerve cells, suggesting possibilities for the prevention and treatment of AD.