• Journal of Applied Biological Chemistry
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• 제63권2호
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• pp.137-145
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• 2020

Oxidative stress is one of the pathogenic mechanisms of various neurodegenerative diseases, such as Alzheimer's disease. Neuroglia, the most abundant cells in the brain, is thought to play an important role in the antioxidant defense system and neuronal metabolic support against neurotoxicity and oxidative stress. We investigated the protective effect of paeoniflorin (PF) against oxidative stress in C6 glial cells. Exposure of C6 glial cells to hydrogen peroxide (H₂O₂, 500 μM) significantly decreased cell viability and increased amounts of lactate dehydrogenase (LDH) release, indicating H₂O₂-induced cellular damage. However, treatment with PF significantly attenuated H₂O₂-induced cell death as shown by increased cell survival and decreased LDH release. The H₂O₂-stimulated reactive oxygen species production was also suppressed, and it may be associated with improvement of superoxide dismutase activity by treatment with PF. In addition, an increase in ratio of Bcl-2/Bax protein expression was observed after treatment with PF. In particular, the down-stream of the apoptotic signaling pathway was inhibited in the presence of PF, mostly by reduction of cleaved-poly ADP ribose polymerase, cleaved caspase-3, and -9 protein expression. Furthermore, H₂O₂-induced phosphorylation of c-Jun N-terminal kinase and extracellular signal-regulated kinase 1/2 was attenuated by treatment with PF. Taken together, neuroprotective effect of PF against oxidative stress probably result from the regulation of apoptotic pathway in C6 glial cells. In conclusion, our findings suggest that PF may be a potent therapeutic agent for neurodegenerative disorders.

• 한국버섯학회지
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• 제12권2호
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• pp.77-81
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• 2014

Mushrooms are considered not only as food but also for source of physiologically beneficial medicines. The culinary-medicinal mushrooms may important role in the prevention of age-associated neurological dysfunctions, including Alzheimer's and Parkinson's diseases. Hericium erinaceus (H. erinaceus), is edible mushrooms, is a parasitic fungus that grows hanging off of logs and trees and well established candidate for brain and nerve health. H. erinaceus contains high amounts of antioxidants, beta-glucan, polysaccharides and a potent catalyst for brain tissue regeneration and helps to improve memory and cognitive functions. Its fruiting bodies and the fungal mycelia exhibit various pharmacological activities, including the enhancement of the immune system, antitumor, hypoglycemic and anti-aging properties. H. erinaceus stimulates the synthesis of Nerve Growth Factor (NGF) which is the primary protein nutrient responsible for enhancing and repairing neurological disorders. Especially hericenones and erinacines isolated from its fruitin body stimulate NGF, synthesis. This fungus is also utilized to regulate blood levels of glucose, triglycerides and cholesterol. H. erinaceus can be considered as useful therapeutic agents in the management and/or treatment of neurodegeneration diseases. However, this review focuses on in vitro, in vivo and clinical trials for neurodegerative disease.

• 대한유전성대사질환학회지
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• 제6권1호
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• pp.108-115
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• 2006

The inherent biology of neural stem cells (NSCs) endows them with capabilities that not only circumvent many of the limitations of other gene transfer vehicles, but that enable a variety of novel therapeutic strategies heretofore regarded as beyond the purview of neural transplantation, Most neurodegenerative diseases are characterized not by discrete, focal abnormalities but rather by extensive, multifocal, or even global neuropathology. Such widely disseminated lesions have not conventionally been regarded as amenable to neural transplantation. However, the ability of NSCs to engraft diffusely and become integral members of structures throughout the host CNS while also expressing therapeutic molecules may permit these cells to address that challenge. Intriguingly, while NSCs can be readily engineered to express specified foreign genes, other intrinsic factors appear to emanate spontaneously from NSCs and, in the context of reciprocal donor-host signaling, seem to be capable of neuroprotective and/or neuroregenerative functions. Stem cells additionally have the appealing ability to "home in" on pathology, even over great distances. Such observations help to advance the idea that NSCs - as a prototype for stem cells from other solid organs - might aid in reconstructing the molecular and cellular milieu of maid eve loped or damaged organs.

• Biomolecules & Therapeutics
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• 제24권1호
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• pp.33-39
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• 2016

Oxidative stress activates several intracellular signaling cascades that may have deleterious effects on neuronal cell survival. Thus, controlling oxidative stress has been suggested as an important strategy for prevention and/or treatment of neurodegenerative diseases. In this study, we found that ginsenoside Rh1 inhibited hydrogen peroxide-induced reactive oxygen species generation and subsequent cell death in rat primary astrocytes. Rh1 increased the expression of phase II antioxidant enzymes, such as heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1, superoxide dismutase-2, and catalase, that are under the control of Nrf2/ARE signaling pathways. Further mechanistic studies showed that Rh1 increased the nuclear translocation and DNA binding of Nrf2 and c-Jun to the antioxidant response element (ARE), and increased the ARE-mediated transcription activities in rat primary astrocytes. Analysis of signaling pathways revealed that MAP kinases are important in HO-1 expression, and act by modulating ARE-mediated transcriptional activity. Therefore, the upregulation of antioxidant enzymes by Rh1 may provide preventive therapeutic potential for various neurodegenerative diseases that are associated with oxidative stress.

• 통합자연과학논문집
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• 제15권4호
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• pp.179-186
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• 2022

The c-Jun N-terminal kinase (JNK3) play major role in neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, cerebral ischemia and other Central Nervous System disorders. Since JNK3 is primarily stated in the brain and stimulated by stress-stimuli, this situation is conceivable that inhibiting JNK3 could be a possible treatment for the mechanisms underlying neurodegenerative diseases. In this study drugs from Zinc15 database were screened to identify the JNK3 inhibitors by Molecular docking and Density functional theory approach. Molecular docking was done by Autodock vina and the ligands were selected based on the binding affinity. Our results identified top ten novel ligands as potential inhibitors against JNK3. Molecular docking revealed that Venetoclax, Fosaprepitant and Avapritinib exhibited better binding affinity and interacting with proposed binding site residues of JNK3. Density functional theory was used to compute the values for energy gap, lowest unoccupied molecular orbital (LUMO), and highest occupied molecular orbital (HOMO). The results of Density functional theory study showed that Venetoclax, Fosaprepitant and Avapritinib serves as a lead compound for the development of JNK3 small molecule 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.

• 대한영상의학회지
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• 제83권3호
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• pp.527-537
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• 2022

철은 중추신경계 및 인체에 필수적인 성분으로 노화 및 다양한 퇴행성 뇌질환에서 뇌의 철 침착이 증가된다. 철은 MRI에서 독특한 특성을 가지고 있어 인체의 철 침착과 분포를 비침 습적으로 평가 및 정량화가 가능하다. 이 종설에서는 철 영상을 위한 MRI 기법에 대하여 알아보고, 노화 및 알츠하이머병을 포함한 퇴행성 뇌질환에서 변화를 고찰해 보고자 한다. 또한 현재 접근법의 제한점과 앞으로 기대되는 새로운 접근도 확인해 보고자 한다.

• BMB Reports
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• 제50권6호
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• pp.299-307
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• 2017

Mitophagy is a process of selective removal of damaged or unnecessary mitochondria using autophagic machinery. Mitophagy plays an essential role in maintaining mitochondrial quality control and homeostasis. Mitochondrial dysfunctions and defective mitophagy in neurodegenerative diseases, cancer, and metabolic diseases indicate a close link between human disease and mitophagy. Furthermore, recent studies showing the involvement of mitophagy in differentiation and development, suggest that mitophagy may play a more active role in controlling cellular functions. A better understanding of mitophagy will provide insights about human disease and offer novel chance for treatment. This review mainly focuses on the recent implications for mitophagy in human diseases and normal physiology.

• Journal of Genetic Medicine
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• 제19권2호
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• pp.49-56
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• 2022

Mitophagy, the selective degradation of damaged or surplus mitochondria using core autophagy machinery, plays an essential role in maintaining cellular mitochondrial function. Impaired mitophagy is closely linked to various human diseases, including neurodegenerative diseases, cardiovascular diseases, cancers and kidney disease. Defective mitophagy induces the accumulation of damaged mitochondria and thereby results in a decline in cellular survival and tissue function. Accordingly, enhancement of mitophagy has been proposed as a novel strategy for the treatment of human diseases closely linked to mitochondrial dysfunction. Recent studies showing that the stimulation of mitophagy has a therapeutic effect on several disease models highlight the possibility of disease treatment using mitophagy. The development of mitophagy inducers with toxicity and the identification of molecular mechanisms will enable the clinical application of mitophagy-based treatments.

• IMMUNE NETWORK
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• 제24권3호
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• pp.20.1-20.21
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• 2024

The brain and lungs, vital organs in the body, play essential roles in maintaining overall well-being and survival. These organs interact through complex and sophisticated bi-directional pathways known as the 'lung-brain axis', facilitated by their close proximity and neural connections. Numerous studies have underscored the mediation of the lung-brain axis by inflammatory responses and hypoxia-induced damage, which are pivotal to the progression of both pulmonary and neurological diseases. This review aims to delve into how pulmonary diseases, including acute/chronic airway diseases and pulmonary conditions, can instigate neurological disorders such as stroke, Alzheimer's disease, and Parkinson's disease. Additionally, we highlight the emerging research on the lung microbiome which, drawing parallels between the gut and lungs in terms of microbiome contents, may play a significant role in modulating brain health. Ultimately, this review paves the way for exciting avenues of future research and therapeutics in addressing respiratory and neurological diseases.