• 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.

• BMB Reports
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• v.43 no.10
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• pp.656-663
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• 2010

Amyloid precursor protein (APP), which is critically involved in the pathogenesis of Alzheimer's disease (AD), is cleaved by gamma/epsilon-secretase activity and results in the generation of different lengths of the APP Intracellular C-terminal Domain (AICD). In spite of its small size and short half-life, AICD has become the focus of studies on AD pathogenesis. Recently, it was demonstrated that AICD binds to different intracellular binding partners ('adaptor protein'), which regulate its stability and cellular localization. In terms of choice of adaptor protein, phosphorylation seems to play an important role. AICD and its various adaptor proteins are thought to take part in various cellular events, including regulation of gene transcription, apoptosis, calcium signaling, growth factor, and $NF-{\kappa}B$ pathway activation, as well as the production, trafficking, and processing of APP, and the modulation of cytoskeletal dynamics. This review discusses the possible roles of AICD in the pathogenesis of neurodegenerative diseases including AD.

• Fisheries and Aquatic Sciences
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• v.21 no.12
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• pp.38.1-38.9
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• 2018

Alzheimer's disease (AD) is a disturbing and advanced neurodegenerative disease and is characterized pathologically by the accumulation of amyloid beta ($A{\beta}$) and the hyperphosphorylation of tau proteins in the brain. The deposition of $A{\beta}$ aggregates triggers synaptic dysfunction, and neurodegeneration, which lead to cognitive disorders. Here, we found that FF isolated from an eatable perennial brown seaweed E.bicyclis protect against $A{\beta}$-induced neurotoxicity in neuroblastoma cells stably transfected with two amyloid precursor protein (APP) constructs: the APP695 cDNA (SH-SY5Y-APP695swe). The FF demonstrated strong inhibitory activity for ${\beta}$-secretase ($IC_{50}$ $16.1{\mu}M$) and its inhibition pattern was investigated using Lineweaver-Burk and Dixon plots, and found to be non-competitive. Then, we tested whether FF could inhibit production of $A{\beta}$ in SH-SY5Y-APP695swe. FF inhibited the production of $A{\beta}$ and soluble-APP, residue of APP from cleaved APP by ${\beta}$-secretase. Our data show that FF can inhibit the production of $A{\beta}$ and soluble-$APP{\beta}$ via inhibition of ${\beta}$-secretase activity. Taken together these results suggest that FF may be worthy of future study as an anti-AD treatment.

• Biomolecules & Therapeutics
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• v.29 no.3
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• pp.290-294
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• 2021

Extracellular beta amyloid (Aβ) plaques are the neuropathological hallmarks of Alzheimer's disease (AD). Accordingly, reducing Aβ levels is considered a promising strategy for AD prevention. 3'-O-acetyl-24-epi-7,8-didehydrocimigenol-3-O-β-D-xylopryranoside significantly decreased the Aβ production and this effect was accompanied with reduced sAPPβ production known as a soluble ectodomain APP fragment through β-secretases in HeLa cells overexpressing amyloid precursor proteins (APPs). This compound also increased the level of sAPPα, which is a proteolytic fragment of APP by α-secretases. In addition, 3'-O-acetyl-24-epi-7,8-didehydrocimigenol-3-O-β-D-xylopryranoside decreased the protein level of β-secretases, but the protein levels of A disintegrin and metalloproteinase (ADAM) family, especially ADAM10 and ADAM17, are increased. Thus, 3'-O-acetyl-24-epi-7,8-didehydrocimigenol-3-O-β-D-xylopryranoside could be useful in the development of AD treatment in the aspect of amyloid pathology.

• 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.

• Journal of Oriental Neuropsychiatry
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• v.18 no.1
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• pp.63-78
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• 2007

Objective : This experiment was designed to investigate the effect of Thalictrum foetidum(TFD) on the Alzheimer's disease. Method : The effects of TFD 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-l 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. Results : The results were summarized as follows ; 1. TFD suppressed APP, AChE, GFAP mRNA in PC-12 cell treated by $A{\beta}$. 2. TFD suppressed $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ mRNA in THP-l cell treated by LPS 3.. TFD suppressed AChE activity in cell lysate of PC-12 cell treated by $A{\beta}$. 4. TFD increased glucose and decreased AChE significantly in the serum of the memory deficit mice induced by scopolamine. 5. TFD group showed significantly inhibitory effect on the scopolamine-induced impairment of learning and memory in the experiment of Morris water maze. Conclusion : According to the above results, it is suggested that TFD might be usefully applied for prevention and treatment of Alzheimer's disease.

• Proceeding of EDISON Challenge
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• 2014.03a
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• pp.237-249
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• 2014

Deposition of amyloid-${\beta}$ ($A{\beta}$) proteins is the conventional pathological hallmark of Alzheimer's disease (AD). The $A{\beta}$ protein formed from the amyloid precursor protein is predominated by the 40 residue protein ($A{\beta}40$) and by the 42 residue protein ($A{\beta}42$). While $A{\beta}40$ and $A{\beta}42$ differ in only two amino acid residues at the C-terminal end, $A{\beta}42$ is much more prone to aggregate and exhibits more neurotoxicity than $A{\beta}40$. Here, we investigate the molecular origin of the difference in the aggregation propensity of these two proteins by performing fully atomistic, explicit-water molecular dynamics simulations. Then, it is followed by the solvation thermodynamic analysis based on the integral-equation theory of liquids. We find that $A{\beta}42$ displays higher tendency to adopt ${\beta}$-sheet conformations than $A{\beta}40$, which would consequently facilitate the conversion to the ${\beta}$-sheet rich fibril structure. Furthermore, the solvation thermodynamic analysis on the simulated protein conformations indicates that $A{\beta}42$ is more hydrophobic than $A{\beta}40$, implying that the surrounding water imparts a larger thermodynamic driving force for the self-assembly of $A{\beta}42$. Taken together, our results provide structural and thermodynamic grounds on why $A{\beta}42$ is more aggregation-prone than $A{\beta}40$ in aqueous environments.

• Journal of Oriental Neuropsychiatry
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• v.13 no.1
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• pp.79-115
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• 2002

This research investigates the effect of the Crataegus pinnatifida BGE. var. major N.E. BR(CPVM) on Alzheimer's disease. Specifically, the effects of the DYHT extract on (1) $IL-1{\beta}$, IL-6, amyloid precursor proteins(APP), acetylcholinesterase(AChE), and glial fibrillary acidic protein(GFAP) mRNA of PC-12 cells treated with CTI05; (2) the AChE activity and the APP production of PC-12 cell treated with CT105; (3) the behavior; and (4) expression of $IL-1{\beta}$, $TNF-{\alpha}$, reactive oxygen species(ROS), nitrite oxide(NO); and (5) the infarction area of the hippocampus, and brain tissue injury in Alzheimer's diseased mice induced with CT105 were investigated. The results are as follow. 1. The CPVM extract suppressed the expression of $IL-1{\beta}$, IL-6, APP, AChE, and GFAP mRNA in PC-12 cells treated with CT105. 2. The CPVM extract suppressed the AChE activity and the production of APP significantly in PC-12 cells treated with CT105. 3. The CPVM extract group showed a significant inhibitory effect on the memory deficit for the mice with Alzheimer's disease induced by CT105 in the Morris water maze experiment. 4. The CPVM extract suppressed the over-expression of $IL-1{\beta}$, $TNF-{\alpha}$, ROS and NO in the mice with Alzheimer's disease induced by CT105. 5. The CPVM extract reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by CT105. These results suggest that the CPVM extract may be effective for the prevention and treatment of Alzheimer's disease.

• Korean Journal of Agricultural Science
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• v.49 no.2
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• pp.227-237
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• 2022

Amyloid beta (Aβ) is produced from an amyloid precursor protein by the activation of the amyloidogenic pathway, and it is widely known to cause Alzheimer's disease (AD). In this study, we investigated the neuroprotective effects of three flavonoids, quercitrin, isoquercitrin, and afzelin, from Acer okamotoanum against Aβ-induced neurotoxicity in SH-SY5Y neuronal cells. Aβ_25-35 treatments resulted in decreased cell viability and increased levels of nuclei condensation and fragmentation. However, an isoquercitrin treatment dose-dependently increased cell viability and decreased nuclei condensation and fragmentation levels. SH-SY5Y cells treated with Aβ_25-35 showed increased reactive oxygen species (ROS) production compared to that from cells not treated with Aβ_25-35. However, treatment with the three flavonoids significantly inhibited ROS production compared to an Aβ_25-35-treated control group, indicating that the three flavonoids blocked neuronal oxidative stress. For a closer examination of the neuroprotective mechanisms, we measured the expressions of the non-amyloidogenic pathway-related proteins of a disintegrin and metalloprotease 10 (ADAM10) and the tumor necrosis factor-α converting enzyme (TACE). An isoquercitrin treatment enhanced the expressions of ADAM10 compared to the control group. In addition, the three flavonoids activated the non-amyloidogenic pathway via the upregulation of TACE. In conclusion, we demonstrated neuroprotective effects of three flavonoids from A. okamotoanum, in particular isoquercitrin, on neurotoxicity by the regulation of the non-amyloidogenic pathway in Aβ_25-35-treated SH-SY5Y cells. Therefore, we suggest that flavonoids from A. okamotoanum may have some potential as therapeutics of AD.

• Journal of Life Science
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• v.22 no.12
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• pp.1608-1613
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• 2012

A conventional kinesin, KIF5/Kinesin-I, transports various cargoes along the microtubule through interaction between its light chain subunit and the cargoes. Kinesin light chains (KLCs) interact with many different cargoes using their tetratricopeptide repeat (TPR) domain, but the mechanism underlying recognition and binding of a specific cargo has not yet been completely elucidated. We used the yeast two-hybrid assay to identify proteins that interact with the TPR domain of KLC1. We found an interaction between the TPR domain of KLC1 and an amyloid precursor protein (APP)-binding protein PAT1 (protein interacting with APP tail 1). The yeast two-hybrid assay demonstrated that the TPR domain-containing region of KLC1 mediated binding to the C-terminal tail region of PAT1. PAT1 also bound to KLC2 but not to kinesin heavy chains (KIF5A, KIF5B, and KIF5C) in the yeast two-hybrid assay. These protein-protein interactions were also observed in the glutathione S-transferase (GST) pull-down assay and by co-immunoprecipitation. Anti-PAT1 antibody as well as anti-APP anti-body co-immunoprecipitated KLC and KHCs associated with PAT1 from mouse brain extracts. These results suggest that PAT1 could mediate interactions between Kinesin-I and APP containing vesicles.