• BMB Reports
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• 제50권7호
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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.

• Journal of Applied Biological Chemistry
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• 제66권
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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.

• 한국약용작물학회:학술대회논문집
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• 한국약용작물학회 2006년도 Spring Conference
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• pp.75-90
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• 2006

Both synthetic and endogenous $A{\beta}$ are degraded by peptidase G. Both $A{\beta}40$ and 42 are cleaved by peptidase G. Peptidase G cleaves $A{\beta}40$ into small fragments ($A{\beta}18$) which lacks aggregation property and are not toxic to neuron. Peptidase G seems to degrade multimeric $A{\beta}$ more efficiently than monomeric $A{\beta}$. Peptidase G protects neurons from toxicity induced by $A{\beta}$ by cleaving it into smaller fragments. Thus, dis-regulation of peptidase G could contribute amyloid deposit found in AD brain.

• Fisheries and Aquatic Sciences
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• 제21권5호
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• pp.13.1-13.8
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• 2018

Amyloid plaque, also called senile plaque, the product of aggregation of ${\beta}$-amyloid peptides ($A{\beta}$), is observed in brains of the patients with Alzheimer's disease (AD) and is one of the key factors in etiology of the disease. In this study, hydrolysates obtained from the sea hare (Aplysia kurodai) were investigated for ${\beta}$-secretase inhibitory peptide. The sea hare's muscle protein was hydrolyzed using six enzymes in a batch reactor. Trypsin hydrolysate had highest ${\beta}$-secretase inhibitory activity compared to the other hydrolysates. ${\beta}$-secretase inhibitory peptide was separated using Sephadex G-25 column chromatography and high-performance liquid chromatography on a C18 column. ${\beta}$-secretase inhibitory peptide was identified as eight amino acid residues of Val-Ala-Ala-Leu-Met-Leu-Phe-Asn by N-terminal amino acid sequence analysis. $IC_{50}$ value of purified ${\beta}$-secretase inhibitory peptide was $74.25{\mu}M$, and Lineweaver-Burk plots suggested that the peptide purified from sea hare muscle protein acts as a competitive inhibitor against ${\beta}$-secretase. Results of this study suggest that peptides derived from sea hare muscle may be beneficial as anti-dementia compounds in functional foods or as pharmaceuticals.

• 대한한의학회지
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• 제29권2호
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• pp.151-164
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• 2008

Objective: To investigate the effects of Yeongdamsagantang (YDGT) on apoptosis of neuronal cells that can result in dementia. Method: The water extract of the YDGT was tested in vitro for its beneficial effects on neuronal survival and neuroprotective functions, particularly in connection with $A{\beta}$ oligomer-related dementias. $A{\beta}$ oligomers derived from proteolytic processing of the ${\beta}-amyloid$ precursor protein (APP), including the $amyloid-{\beta}$ peptide $(A{\beta})$, play a critical role in the pathogenesis of Alzheimer's disease. A neuroblastoma cell line stably expressing an $A{\beta}$ oligomerassociated neuronal degeneration was used to investigate if YDGT inhibits formation of $A{\beta}$ oligomer. To measure the ATP generating level in mitochondrial membrane, luciferin/luciferase luminescence kit (Promega) and luminator was used, and to survey the protein's apparition, confocal microscopy was used. Result: $A{\beta}oligomer$ had a profound attenuation in the increase in CT105 expressing neuro2A cells from YDGT. Experimental evidence indicates that YDGT protected against neuronal damage from cells, but its cellular and molecular mechanisms remain unknown. We demonstrated that YDGT inhibited formation of $amyloid-{\beta}$ $(A{\beta})$ oligomers, which were the behavior, and possibly causative, features of AD. The decreased $A{\beta}$ oligomer in the presence of YDGT was observed in the conditioned medium of this $A{\beta}oligomer-secreting$ cell line under in vitro. In the cells, YDGT significantly attenuated mitochondrion-initiated apoptosis. Conclusion: (i) a direct $A{\beta}$ oligomer toxicity and the apoptosis initiated by the mitochondria; and (ii) multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of $A{\beta}$ oligomer aggregation, underlie the neuroprotective effects of YDGT.

• 생물정신의학
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• 제8권1호
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• pp.62-70
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• 2001

Alzheimer's disease(AD) is associated with a characteristic neuropathology. The major hallmarks of AD are senile plaques (SPs) and neurofibrillary tangles(NFTs). ${\beta}$-amyloid protein($A{\beta}$) is derived from the proteolysis of amyloid precursor protein(APP) and then converted to SPs. Mature SPs produce cytotoxicity through direct toxic effects and activation of microglia and complement. NFTs are composed of paired helical filaments(PHFs) including abnormally phosphorylated form of the microtubule-associated protein(MAP) tau and increased tau level in cerebrospinal fluid may be observed in most AD. The aggregation of $A{\beta}$ and tau formation are thought to be a final common pathway of AD. Acetylcholine, dopamine, serotonin, GABA and their receptors are associated with AD. Especially, decreased nicotinic acetylcholine receptors(nAChRs) in AD are reported. Genetic lesions associated with AD are mutations in the structural genes for the APP located on chromosome 21, presenilin(PSN)1 located on chromosome 14 and PSN2 located on chromosome 1. Also, trisomy 21, Apo-E gene located on chromosome 19, PMF locus, low density lipoprotein receptor-related protein and ${\alpha}$-macroglobulin increase risk of AD. In this article, we will review about the neurobiology of AD and some newly developed research areas.

• Molecules and Cells
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• 제24권1호
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• pp.69-75
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• 2007

Alzheimer's disease is a neurodegenerative disorder associated with progressive loss of cognitive function and memory. Amyloid beta peptide ($A{\beta}$) is the major component of senile plaques and is known to exert its cytotoxic effect mainly by producing $H_2O_2$. Vascular endothelial growth factor (VEGF) is elevated in the cerebrospinal fluid (CSF) and brain of AD patients, and $H_2O_2$ is one of the factors that induce VEGF. Therefore, we tested whether $A{\beta}$ might be responsible for the increased VEGF synthesis. We found that $A{\beta}$ induced the production of $H_2O_2$ in vitro. Comparison of the amount of $H_2O_2$ required to induce VEGF synthesis in HN33 cells and the amount of $H_2O_2$ produced by $10{\mu}M\;A{\beta}_{1-42}$ in vitro suggested that a toxic concentration of $A{\beta}$ might induce VEGF synthesis in these cells. However, toxic concentrations of $A{\beta}$ failed to induce VEGF synthesis in several cell systems. They also had no effect on antioxidant enzymes such as glutathione peroxidase, catalase, and peroxiredoxin in HN33 cells. $Cu^{2+}$, $Zn^{2+}$ and $Fe^{3+}$ are known to accumulate in the brains of AD patients and promote aggregation of $A{\beta}$, and $Cu^{2+}$ by itself induces synthesis of VEGF. However, there was no synergistic effect between $Cu^{2+}$ and $A{\beta}_{1-42}$ in the induction of VEGF synthesis and $Zn^{2+}$ and $Fe^{3+}$ also had no effect on the synthesis of VEGF, alone or in combination with $A{\beta}$.

• Bulletin of the Korean Chemical Society
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• 제25권6호
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• pp.838-842
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• 2004

Amyloid peptide (A${\beta}$) is the major component of senile plaques found in the brain of patient of Alzheimer's disease. ${\beta}$-amyloid peptide (25-35) (A${\beta}$25-35) is biologically active fragment of A${\beta}$. The three-dimensional structure of A${\beta}$25-35 in aqueous solution with 50% (vol/vol) TFE determined by NMR spectroscopy previously adopts an ${\alpha}$-helical conformation from $Ala^{30}$ to $Met^{35}$. It has been proposed that A${\beta}$(25-35) exhibits pH- and concentration-dependent ${\alpha}-helix{\leftrightarrow}{\beta}$sheet transition. This conformational transition with concomitant peptide aggregation is a possible mechanism of plaque formation. Here, in order to gain more insight into the mechanism of ${\alpha}$-helix formation of A${\beta}$25-35 peptide by TFE, which particularly stabilizes ${\alpha}$-helical conformation, we studied the secondary-structural elements of A${\beta}$25-35 peptide by molecular dynamics simulations. Secondary structural elements determined from NMR spectroscopy in aqueous TFE solution are preserved during the MD simulation. TFE/water mixed solvent has reduced capacity for forming hydrogen bond to the peptide compared to pure water solvent. TFE allows A${\beta}$25-35 to form bifurcated hydrogen bonds to TFE as well as to residues in peptide itself. MD simulation in this study supports the notion that TFE can act as an ${\alpha}$-helical structure forming solvent.

• 대한한방내과학회지
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• 제27권3호
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• pp.603-616
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• 2006

The water extract of Gamiyaengshinhwan (GYH), has been used in vitro tests for its beneficial effects on neuronal survival and neuroprotective functions, particularly in connection with CT105-related dementias and Alzheimer's disease(AD). CT105 derived from proteolytic processing of the $\beta$-amyloid precursor protein (APP), including the amyloid-$\beta$ peptide ($A{\beta}$), plays a critical role in the pathogenesis of Alzheimer's dementia. We determined that transfected overexpressing APP695 and $A{\beta}$ CT105 have a profound attenuation in the Increase in CT105 expressing neuro2A cells from GYH. Experimental evidence indicates that GYH protects against neuronal damage from cells, but its cellular and molecular mechanisms remain unknown. Using a neuroblastoma cell line stably expressing CT105-associated neuronal degeneration, we demonstrated that GYH inhibits formation of amyloid-$\beta$ fragment ($A{\beta}$ CT105). which are the characteristic, and possibly causative, features of AD. The decreased CT105 $A{\beta}$ in the presence of GYH was observed in the conditioned medium of this CT105-secreting cell line under in vitro. In the cells, GYH significantly attenuated mitochondrion-initiated apoptosis and decreased the activity of Bax, a key enzyme in the apoptosis cell-signaling cascade. These results suggest that neuronal damage in AD might be due to two factors: a direct CT05 toxicity and the apoptosis initiated by the mitochondria. Multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of CT105 aggregation, underlie the neuroprotective effects of GYH.

• 한국키틴키토산학회지
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• 제23권4호
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• pp.220-227
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• 2018

Amyloid plaque is a product of aggregation of ${\beta}$-amyloid peptide ($A{\beta}$) and is an important factor in the pathogenesis of Alzheimer's Disease (AD). $A{\beta}$ is a major component of amyloid plaque and vascular deposits in the AD brain. The enzyme ${\beta}$-secretase is required for the production of $A{\beta}$; thus, prevention of the formation of $A{\beta}$ through the inhibition of ${\beta}$-secretase is a major focus in the study of the treatment of AD. In this study, we investigated ${\beta}$-secretase inhibitory activity of an Arctoscopus japonicus peptide. An Alcalase hydrolysate had the highest ${\beta}$-secretase inhibitory activity. A ${\beta}$-secretase inhibitory activity peptide was separated using ion exchange column chromatography (carboxy-methyl: CM, quaternary methyl ammonium: QMA) and reverse phase high performance liquid chromatography (RP-HPLC) on a C18 column. The $IC_{50}$ value of the purified peptide was $248.2{\pm}1.73{\mu}g/mL$. The ${\beta}$-secretase inhibitory peptide was identified as a six amino acid residue of Gly-Pro-Val-Gly-Ala-Pro (MW: 497.27 Da). In cell viability experiments, the final purified fraction, the carboxy-methyl ion exchange column fraction (CM-F1) showed no significant cytotoxic effect in SH-SY5Y cells at concentrations below $100{\mu}g/mL$ in 24 h. The results of this study suggest that peptides separated from Arctoscopus japonicus may be beneficial as ${\beta}$-secretase inhibitor compounds in functional foods.