• Biomolecules & Therapeutics
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• 제31권4호
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• pp.417-424
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• 2023

Parkinson's disease (PD) which has various pathological mechanisms, recently, it is attracting attention to the mechanism via microbiome-gut-brain axis. 6-Shogaol, a representative compound of ginger, have been known for improving PD phenotypes by reducing neuroinflammatory responses. In the present study, we investigated whether 6-shogaol and ginger attenuate degeneration induced by Proteus mirabilis (P. mirabilis) on the intestine and brain, simultaneously. C57BL/6J mice received P. mirabilis for 5 days. Ginger (300 mg/kg) and 6-shogaol (10 mg/kg) were treated by gavage feeding for 22 days including the period of P. mirabilis treatment. Results showed that 6-shogaol and ginger improved motor dysfunction and dopaminergic neuronal death induced by P. mirabilis treatment. In addition, they suppressed P. mirabilis-induced intestinal barrier disruption, pro-inflammatory signals such as toll-like receptor and TNF-α, and intestinal α-synuclein aggregation. Moreover, ginger and 6-shogaol significantly inhibited neuroinflammation and α-synuclein in the brain. Taken together, 6-shogaol and ginger have the potential to ameliorate PD-like motor behavior and degeneration of dopaminergic neurons induced by P. mirabilis in mice. Here, these findings are meaningful in that they provide the first experimental evidence that 6-shogaol might attenuate PD via regulating gut-brain axis.

• Biomolecules & Therapeutics
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• 제26권4호
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• pp.350-357
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• 2018

Glial cells are receiving much attention since they have been recognized as important regulators of many aspects of brain function and disease. Recent evidence has revealed that two different glial cells, astrocytes and microglia, control synapse elimination under normal and pathological conditions via phagocytosis. Astrocytes use the MEGF10 and MERTK phagocytic pathways, and microglia use the classical complement pathway to recognize and eliminate unwanted synapses. Notably, glial phagocytosis also contributes to the clearance of disease-specific protein aggregates, such as ${\beta}$-amyloid, huntingtin, and ${\alpha}$-synuclein. Here we reivew recent findings showing that glial cells are active regulators in brain functions through phagocytosis and that changes in glial phagocytosis contribute to the pathogenesis of various neurodegenerative diseases. A better understanding of the cellular and molecular mechanisms of glial phagocytosis in healthy and diseased brains will greatly improve our current approach in treating these diseases.

• 한국정보처리학회:학술대회논문집
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• 한국정보처리학회 2014년도 춘계학술발표대회
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• pp.753-756
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• 2014

파킨슨병은 도파민계 신경이 파괴되는 질병으로 알츠하이머병과 함께 대표적인 퇴행성 뇌 질환으로 병의 진행을 완화시킬 수 있는 치료법이 존재하기 때문에 병의 진단이 굉장히 중요하다. 파킨슨병을 진단하기 위한 과거의 연구는 대부분 단일 생체지표를 이용하는 것이었지만 이러한 방법에는 한계성이 존재한다. 따라서 본 연구에서는 생화학적 생체지표인 뇌척수액 내의 ${\alpha}-synuclein$ 단백질 수치와 영상학적 생체지표인 확산 텐서 영상의 여러 모수들을 결합한 융합 생체지표를 특징으로 사용하는 파킨슨병 진단 모델을 개발하고 성능을 평가하였다. 10-fold cross validation 에서 모든 성능지표에 대해 최고 100%를 보였으며, cross validation 의 과적합을 감안하더라도 파킨슨병의 조기진단에 유용하게 사용될 수 있는 가능성을 제시하였다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권16호
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• pp.6949-6954
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• 2014

Background: Recent studies have indicated that microRNA-15a (miR-15a) is dysregulated in breast cancer (BC). We aimed to evaluate the expression of miR-15a in BC tissues and corresponding para-carcinoma tissues. We also focused on effects of miR-15a on cellular behavior of MDA-MB-231 and expression of its target gene synuclein-${\gamma}$ (SNCG). Materials and Methods: The expression levels of miR-15a were analysed in BC formalin fixed paraffin embedded (FFPE) tissues by microarray and quantitative real-time PCR. CCK-8 assays, cell cycle and apoptosis assays were used to explore the potential functions of miR-15a in MDA-MB-231 human BC cells. A luciferase reporter assay confirmed direct targets. Results: Downregulation of miR-15a was detected in most primary BCs. Ectopic expression of miR-15a promoted proliferation and suppressed apoptosis in vivo. Further studies indicated that miR-15a may directly interact with the 3'-untranslated region (3'-UTR) of SNCG mRNA, downregulating its mRNA and protein expression levels. SNCG expression was negatively correlated with miR-15a expression. Conclusions: MiR-15a has a critical role in mediating cell cycle arrest and promoting cell apoptosis of BC, probably by directly targeting SNCG. Thus, it may be involved in development and progression of BC.

• 한국응용과학기술학회지
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• 제41권1호
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• pp.58-68
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• 2024

본 연구의 목적은 알츠하이머질환(Alzheimer's disease: AD) 동물 모델을 대상으로 트레드밀 운동(Treadmill exercise: TE)과 환경강화(environmental enrichment: EE) 처치가 인지기능, 근 기능, 및 밀착연접 단백질 발현에 미치는 영향을 확인하는데 있다. AD 동물 모델을 제작하기 위해 aluminum chloride(AlCl₃)를 90일간(40mg/kg/하루) 투여 하였으며 동시에 TE(10-12m/min, 40-60min/day) 혹은 EE에 노출시켰다. 그 결과 AlCl₃ 투여에 의한 인지기능 저하와 근 기능 감소가 TE와 EE에 의해 완화된 것으로 나타났다. 또한, TE와 EE는 AD 질환에서 나타나는 β-amyloid(Aβ), alpha-synuclein 및 tumor necrosis factor-α(TNF-α) 단백질의 발현 증가를 감소시킨 것으로 나타났다. 게다가 TE와 EE는 AlCl₃ 투여에 의해 감소된 밀착연접 단백질(Occludin, Claudin-5 및 ZO-1)의 발현을 통계적으로 유의하게 증가시킨 것으로 나타났다. 마지막으로 Aβ 단백질과 밀착연접 단백질과의 상관분석을 실시한 결과 부적 상관관계(Occludin: r=-0.853, p=0.001; Claudin-5 : r=-0.352, p=0.915; ZO-1 : r=-0.424, p=0.0390)로 나타났다. 따라서 이를 종합해 보면 TE 혹은 EE 처치는 AD에 나타나는 병리학적 특징들을 일부 완화시켜 인지기능과 근 기능을 일부 개선 시킬 수 있는 효과적인 운동 방법이라고 생각된다.

• BMB Reports
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• 제42권9호
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• pp.541-551
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• 2009

Amyloidogenesis defines a condition in which a soluble and innocuous protein turns to insoluble protein aggregates known as amyloid fibrils. This protein suprastructure derived via chemically specific molecular self-assembly process has been commonly observed in various neurodegenerative disorders such as Alzheimer's, Parkinson's, and Prion diseases. Although the major culprit for the cellular degeneration in the diseases remains unsettled, amyloidogenesis is considered to be etiologically involved. Recent recognition of fibrillar polymorphism observed mostly from in vitro amyloidogeneses may indicate that multiple mechanisms for the amyloid fibril formation would be operated. Nucleation-dependent fibrillation is the prevalent model for assessing the self-assembly process. Following thermodynamically unfavorable seed formation, monomeric polypeptides bind to the seeds by exerting structural adjustments to the template, which leads to accelerated amyloid fibril formation. In this review, we propose another in vitro model of amyloidogenesis named double-concerted fibrillation. Here, two consecutive assembly processes of monomers and subsequent oligomeric species are responsible for the amyloid fibril formation of $\alpha$-synuclein, a pathological component of Parkinson's disease, following structural rearrangement within the oligomers which then act as a growing unit for the fibrillation.

• Biomolecules & Therapeutics
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• 제20권2호
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• pp.133-143
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• 2012

Matrix metalloproteinases (MMPs) are a subfamily of zinc-dependent proteases that are re-sponsible for degradation and remodeling of extracellular matrix proteins. The activity of MMPs is tightly regulated at several levels including cleavage of prodomain, allosteric activation, com-partmentalization and complex formation with tissue inhibitor of metalloproteinases (TIMPs). In the central nervous system (CNS), MMPs play a wide variety of roles ranging from brain devel-opment, synaptic plasticity and repair after injury to the pathogenesis of various brain disorders. Following general discussion on the domain structure and the regulation of activity of MMPs, we emphasize their implication in various brain disorder conditions such as Alzheimer's disease, multiple sclerosis, ischemia/reperfusion and Parkinson's disease. We further highlight accumu-lating evidence that MMPs might be the culprit in Parkinson's disease (PD). Among them, MMP-3 appears to be involved in a range of pathogenesis processes in PD including neuroinflamma-tion, apoptosis and degradation of ${\alpha}$-synuclein and DJ-1. MMP inhibitors could represent poten-tial novel therapeutic strategies for treatments of neurodegenerative diseases.

• BMB Reports
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• 제51권1호
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• pp.5-13
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• 2018

Formation of toxic protein aggregates is a common feature and mainly contributes to the pathogenesis of neurodegenerative diseases (NDDs), which include amyotrophic lateral sclerosis (ALS), Alzheimer's, Parkinson's, Huntington's, and prion diseases. The transglutaminase 2 (TG2) gene encodes a multifunctional enzyme, displaying four types of activity, such as transamidation, GTPase, protein disulfide isomerase, and protein kinase activities. Many studies demonstrated that the calcium-dependent transamidation activity of TG2 affects the formation of insoluble and toxic amyloid aggregates that mainly consisted of NDD-related proteins. So far, many important and NDD-related substrates of TG2 have been identified, including $amlyoid-{\beta}$, tau, ${\alpha}-synuclein$, mutant huntingtin, and ALS-linked trans-activation response (TAR) DNA-binding protein 43. Recently, the formation of toxic inclusions mediated by several TG2 substrates were efficiently inhibited by TG2 inhibitors. Therefore, the development of highly specific TG2 inhibitors would be an important tool in alleviating the progression of TG2-related brain disorders. In this review, the authors discuss recent advances in TG2 biochemistry, several mechanisms of molecular regulation and pleotropic signaling functions, and the presumed role of TG2 in the progression of many NDDs.

• 대한의생명과학회지
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• 제29권3호
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• pp.121-129
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• 2023

Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects millions of people worldwide. The conventional treatment model for PD have harmful side effects, such as dyskinesia, hallucinations, nausea, and fatigue, and are expensive. As a result, natural products derived from medicinal herbs, fruits, and vegetables have emerged as potential therapeutic strategies for PD. These natural products have been traditionally used to treat various diseases and have been shown to possess anti-oxidative and anti-inflammatory properties, as well as inhibitory roles in protein misfolding, mitochondrial homeostasis, neuroinflammation and other neuroprotective processes. In addition, they have fewer side effects and are generally less expensive than conventional drugs. It also discusses the limitations of current treatments and the potential of natural remedies derived from plants to treat PD in new ways or as supplements to existing treatments. The multifunctional mechanisms of medicinal plants that may be utilized to treat PD are also discussed, including the modulation of neurotransmitter systems, the enhancement of neurotrophic factors, and the inhibition of apoptosis. While more research is needed to fully understand their mechanisms of action and efficacy, natural products have the potential to provide safer and more effective treatment options for patients with PD.

• 대한한방내과학회지
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• 제33권1호
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• pp.102-110
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• 2012

Multiple system atrophy (MSA) is a sporadic progressive neurodegenerative disorder characterized clinically by various combinations of parkinsonian, autonomic, cerebellar, or pyramidal signs and pathologically by cell loss, gliosis, and ${\alpha}$-synuclein-positive glial cytoplasmic inclusions in several brain and spinal cord structures. This is a clinical report about a 69-year-old female who had MSA treated by oriental medical treatment and evaluated by Unified Multiple System Atrophy Rating Scale (UMSARS). The patient was treated with herb medicine Chungsimyeonj-aeumgami(淸心蓮子飮加味), acupuncture, moxibustion and cupping. After treatment, the patient's symptoms improved meaningfully and the score decreased in UMSARS Part I, II. This suggests that oriental medical treatment could be effective to improve MSA patients' symptoms. It is necessary to have more observations and many cases of patients with MSA.