• The Korean Journal of Food & Health Convergence
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• v.4 no.4
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• pp.18-25
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• 2018

Proteins play a key role in many functions such as metabolic activity, differentiation, as cargos and cell fate regulators. It is necessary to know about the markers involved in male fertility in order to develop remedies for the treatment of male infertility. But, the role of the proteins is not limited to particular function in the biological systems. Some of the proteins act as ion channels such as catsper and proteins like Nanos acts as a translational repressor in germ cells and expressed in prenatal period whose role in male fertility is uncertain. Rbm5 is a pre mRNA splicing factor necessary for sperm differentiation whose loss of function results deficit in sperm production. DEFB114 is a beta defensin family protein necessary for sperm motility in LPS challenged mice where as TEX 101 is a plasma membrane specific germ cell protein whose function is not clearly known u to now. Gpr56 is another adhesion protein whose null mutation leads to arrest of production of pups in rats. Amyloid precursor protein role in Alzheimer's disease is already known but it plays an important role in male fertility also but its function is uncertain and has to be considered while targeting APP during the treatment of Alzheimer's disease. The study on amyloid precursor protein in male fertility is a novel thing but requires further study in correlation to alzheimer's disease.

• Journal of Ginseng Research
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• v.41 no.4
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• pp.566-571
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• 2017

Background: A number of reports have described the protective effects of ginsenoside Rg1 (Rg1) in Alzheimer's disease (AD). However, the protective mechanisms of Rg1 in AD remain elusive. Methods: To investigate the potential mechanisms of Rg1 in ${\beta}$-amyloid peptide-treated SH-SY5Y cells, a comparative proteomic analysis was performed using stable isotope labeling with amino acids in cell culture combined with nano-LC-MS/MS. Results: We identified a total of 1,149 proteins in three independent experiments. Forty-nine proteins were significantly altered by Rg1 after exposure of the cells to ${\beta}$-amyloid peptides. The protein interaction network analysis showed that these altered proteins were clustered in ribosomal proteins, mitochondria, the actin cytoskeleton, and splicing proteins. Among these proteins, mitochondrial proteins containing HSD17B10, AARS2, TOMM40, VDAC1, COX5A, and NDUFA4 were associated with mitochondrial dysfunction in the pathogenesis of AD. Conclusion: Our results suggest that mitochondrial proteins may be related to the protective mechanisms of Rg1 in AD.

• BMB Reports
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• v.50 no.7
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• pp.345-354
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• 2017

Autophagy, a catabolic process necessary for the maintenance of intracellular homeostasis, has recently been the focus of numerous human diseases and conditions, such as aging, cancer, development, immunity, longevity, and neurodegeneration. However, the continued presence of autophagy is essential for cell survival and dysfunctional autophagy is thought to speed up the progression of neurodegeneration. The actual molecular mechanism behind the progression of dysfunctional autophagy is not yet fully understood. Emerging evidence suggests that basal autophagy is necessary for the removal of misfolded, aggregated proteins and damaged cellular organelles through lysosomal mediated degradation. Physiologically, neurodegenerative disorders are related to the accumulation of amyloid ${\beta}$ peptide and ${\alpha}-synuclein$ protein aggregation, as seen in patients with Alzheimer's disease and Parkinson's disease, respectively. Even though autophagy could impact several facets of human biology and disease, it generally functions as a clearance for toxic proteins in the brain, which contributes novel insight into the pathophysiological understanding of neurodegenerative disorders. In particular, several studies demonstrate that natural compounds or small molecule autophagy enhancer stimuli are essential in the clearance of amyloid ${\beta}$ and ${\alpha}-synuclein$ deposits. Therefore, this review briefly deliberates on the recent implications of autophagy in neurodegenerative disorder control, and emphasizes the opportunities and potential therapeutic application of applied autophagy.

• Molecules and Cells
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• v.40 no.1
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• pp.73-81
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• 2017

The ${\gamma}$-secretase complex represents an evolutionarily conserved family of transmembrane aspartyl proteases that cleave numerous type-I membrane proteins, including the ${\beta}$-amyloid precursor protein (APP) and the receptor Notch. All known rare mutations in APP and the ${\gamma}$-secretase catalytic component, presenilin, which lead to increased amyloid ${\beta}$-peptide production, are responsible for early-onset familial Alzheimer's disease. ${\beta}$-amyloid protein precursor-like (APPL) is the Drosophila ortholog of human APP. Here, we created Notch- and APPL-based Drosophila reporter systems for in vivo monitoring of ${\gamma}$-secretase activity. Ectopic expression of the Notch- and APPL-based chimeric reporters in wings results in vein truncation phenotypes. Reporter-mediated vein truncation phenotypes are enhanced by the Notch gain-of-function allele and suppressed by RNAi-mediated knockdown of presenilin. Furthermore, we find that apoptosis partly contributes to the vein truncation phenotypes of the APPL-based reporter, but not to the vein truncation phenotypes of the Notch-based reporter. Taken together, these results suggest that both in vivo reporter systems provide a powerful genetic tool to identify genes that modulate ${\gamma}$-secretase activity and/or APPL metabolism.

• The Journal of Internal Korean Medicine
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• v.22 no.3
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• pp.331-339
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• 2001

목적 : 본 연구는 식풍해경(熄風解痙), 소산풍열(疏散風熱) 효능이 있는 백강잠이 치매에 미치는 영향을 알아보기 위하여 실험을 행하였다. 방법 : 치매 유발물질인 $amyloid{\beta}(A{\beta})$ 25-35를 흰쥐의 뇌 astrocyte에 처리한 후 대표적인 항산화 효소인 catalase, superoxide dismutase,glutathione peroxidase 및 glutathione-S-transferase의 활성 변화와 NO 생성 변화를 관찰하였다. 결과 $A{\beta}$ 25-35 처리로 catalase와 superoxide dismutase 활성이 현저히 감소하였으나 백강잠을 처리한 경우는 이들 효소 활성이 크게 증가하였다. 그리고, $A{\beta}$ 25-35의 농도에 의존적으로 증가된 NO 생성은 백강잠의 농도에 의존적으로 유의성 있게 억제되는 것으로 나타났다. 결론 : 백강잠은 항산화계 효소의 활성화 및 $A{\beta}$처리와 같은 치매유발 물질의 독성에 대한 적응능력 향상을 통하여 astrocyte를 보호하는 효능을 가지는 것으로 사료되며, 아울러 노인성 치매 등 임상적 응용에 그 효과가 기대된다.

• Journal of Oriental Neuropsychiatry
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• v.19 no.1
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• pp.29-42
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• 2008

Objectives : This study was performed to examine the effect of Sinchim on enhancing of memory in rat with water maze. Methods : Experimental animals(white rat) were classfied into normal, control, and aroma sample group. Then, they were injected .{\beta}-amyloid into control and aroma sample group rat's brain about $5{\mu}l$ to injure its brain. After rat smelt Sinchim about 12days, I did water maze test and anatomized its hippocampus. Sections were cut coronally at 30 ${\mu}m$.(XI00) Results: 1. In acquisition test of water maze learning, .{\beta}-amyloid injured group took more time than normal group to reach the escape platform noticeably and through the session of trial, Sinchim aroma sample group shortened time than .l3-amyloid injured group after 6 days. 2. In the acetyltransferase(AchE) immunostained method, it was shown that Sinchim aroma sample recovered tbe syntbesis of ChAT(Choloneacetyltransferase). Conclusion: Smelling Sinchim would be useful for enhancing of memory.

• Animal cells and systems
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• v.5 no.2
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• pp.139-143
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• 2001

Alzheimer's disease is the most common form of dementia and no cure is known so far. Extensive genetic works and in vitro experiments combined with clinical observations link amyloid $\beta$--protein (A$\beta$-) to the pathogenesis of Alzheimer's disease (AD). It was hypothesized that $A\beta$- becomes toxic when it adopts a fibrillar conformation. Recently, non-fibrillar form of $A\beta$- was observed and the potential role in the pathogenesis of AD became an interesting subject. In this study, the cytotoxicity of non-fibrillar $A\beta$- and fibrillar $A\beta$- was compared on oxidative stress, membrane damage, or nucleosome break down. Non-fibrillar $A\beta$- was not toxic in peripheral nervous system-derived cells but significantly toxic in central nervous system-derived cells while fibrillar $A\beta$- was non-selectively toxic in both cell culture. The neurotoxicity of non-fibrillar $A\beta$- was reproduced in semi-in vivo culture of mouse brain slice. In conclusion, non-fibrillar $A\beta$- could be more relevant to the selective neurodegeneration in Alzheimer's brains than fibrillar $A\beta$- and further research needs to be done for identification of the cause of AD.

• Journal of the Korean Society of Radiology
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• v.83 no.3
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• pp.453-472
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• 2022

Over the past decades, the immense clinical need for early detection methods and treatments for dementia has become a priority worldwide. The advances in PET biomarkers play increasingly important roles in understanding disease mechanisms by demonstrating the protein pathology underlying dementia in the brain. Amyloid-β and tau deposition in PET images are now key diagnostic biomarkers for the Alzheimer's disease continuum. The inclusion of biomarkers in the diagnostic criteria has achieved a paradigm shift in facilitating early differential diagnosis, predicting disease prognosis, and influencing clinical management. Furthermore, in vivo images showing pathology could become prognostic as well as surrogate biomarkers in therapeutic trials. In this review, we focus on recent developments in radiotracers for amyloid-β and tau PET imaging in Alzheimer's disease and other neurodegenerative diseases. Further, we introduce their potential application as future perspectives.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.408-415
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• 2023

Alzheimer's disease constitutes a large proportion of all neurodegenerative diseases and is mainly caused by excess aggregation of amyloid beta (Aβ), which results in oxidative stress, inflammation, and apoptosis in the neurons. Populus tomentiglandulosa belongs to the Salicaceae family and is widely distributed in Korea; the antioxidant activities of the extract and fractions from P. tomentiglandulosa have been demonstrated in previous studies. Specifically, the ethyl acetate (EtOAc) fraction of P. tomentiglandulosa (EtOAc-PT) shows the most powerful antioxidative activity. Therefore, the present study investigates the protective effects of EtOAc-PT against neuronal damage in Aβ_25-35-stimulated SH-SY5Y cells. EtOAc-PT restored cell viability significantly as well as inhibited the levels of reactive oxygen species and lactate dehydrogenase release compared to the Aβ_25-35-induced control group. Furthermore, the inflammation- and apoptosis-related protein expressions were investigated to demonstrate its neuroprotective mechanism. EtOAc-PT downmodulated the expressions of inducible nitric oxide synthase, cyclooxygenase-2, B-cell lymphoma 2 associated X, and B-cell lymphoma 2. Thus, the findings show that EtOAc-PT has protective effects against Aβ_25-35 by suppressing oxidative stress, inflammation, and apoptosis.

• Molecular & Cellular Toxicology
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• v.4 no.2
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• pp.157-163
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• 2008

Formation of ${\beta}$-amyloid $(A{\beta})$ fibrils has been identified as one of the major characteristics of Alzheimer's disease (AD). Inhibition of $A{\beta}$ fibril formation in the CNS would be attractive therapeutic targets for the treatment of AD. Several small compounds that inhibit amyloid formation or amyloid neurotoxicity in vitro have been known. Citrate has surfactant function effect because of its molecular structure having high anionic charge density, in addition to the well-known antibacterial and antioxidant properties. Therefore, we hypothesized that citrate might have the inhibitory effect against $A{\beta}$ fibril formation in vitro and have the protective effect against $A{\beta}$-induced neurotoxicity in PC12 cells. We examined the effect of citrate against the formation of $A{\beta}$ fibrils by measuring the intensity of fluorescence in thioflavin-T (Th-T) assay of between $A{\beta}_{25-35}$ groups treated with citrate and the control with $A{\beta}_{25-35}$ alone. The neuroprotective effect of citrate against $A{\beta}$-induced toxicity in PC12 cells was investigated using the WST-1 assay. Fluorescence spectroscopy showed that citrate inhibited dose-dependently the formation of $A{\beta}$ fibrils from ${\beta}$-amyloid peptides. The inhibition percentages of $A{\beta}$ fibril formation by citrate (1, 2.5, and 5 mM) were 31%, 60%, and 68% at 7 days, respectively in thioflavin-T (Th-T) assay. WST-1 assay revealed that the toxic effect of $A{\beta}_{25-35}$ was reduced, in a dose-dependent manner to citrate. The percentages of neuroprotection by citrate (1, 2.5, and 5 mM) against $A{\beta}-induced$ toxicity were 19%, 31 %, and 34%, respectively. We report that citrate inhibits the formation of $A{\beta}$ fibrils in vitro and has neuroprotective effect against $A{\beta}$-induced toxicity in PC12 cells. Neuroprotective effects of citrate against $A{\beta}$ might be, to some extent, attributable to its inhibition of $A{\beta}$ fibril formation. Although the mechanism of anti-amyloidogenic activity is not clear, the possible mechanism is that citrate might have two effects, salting-in and surfactant effects. These results suggest that citrate could be of potential therapeutic value in Alzheimer's disease.