• Biomolecules & Therapeutics
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• 제32권4호
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• pp.403-423
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• 2024

The human gastrointestinal (GI) tract houses a diverse microbial community, known as the gut microbiome comprising bacteria, viruses, fungi, and protozoa. The gut microbiome plays a crucial role in maintaining the body's equilibrium and has recently been discovered to influence the functioning of the central nervous system (CNS). The communication between the nervous system and the GI tract occurs through a two-way network called the gut-brain axis. The nervous system and the GI tract can modulate each other through activated neuronal cells, the immune system, and metabolites produced by the gut microbiome. Extensive research both in preclinical and clinical realms, has highlighted the complex relationship between the gut and diseases associated with the CNS, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This review aims to delineate receptor and target enzymes linked with gut microbiota metabolites and explore their specific roles within the brain, particularly their impact on CNS-related diseases.

• BMB Reports
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• 제42권7호
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• pp.444-449
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• 2009

Different neurodegenerative disorders like prion disease, is caused by protein misfolding conformers. Reverse-transfected cytosolic prion protein (PrP) and PrP expressed in the cytosol have been shown to be neurotoxic. To investigate the possible mechanism of neurotoxicity due to accumulation of PrP in cytosol, a PrP mutant lacking the signal and GPI (CytoPrP) was introduced into the SH-SY5Y cell. MTT and trypan blue assays indicated that the viability of cells expressing CytoPrP was remarkably reduced after treatment of MG-132. Obvious apoptosis phenomena were detected in the cells accumulated with CytoPrP, including loss of mitochondrial transmembrane potential, increase of caspase-3 activity, more annexin V/PI-double positive-stained cells and reduced Bcl-2 level. Moreover, DNA fragmentation and TUNEL assays also revealed clear evidences of late apoptosis in the cells accumulated CytoPrP. These data suggest that the accumulation of CytoPrP in cytoplasm may trigger cell apoptosis, in which mitochondrial relative apoptosis pathway seems to play critical role.

• Journal of Acupuncture Research
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• 제23권3호
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• pp.103-115
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• 2006

Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disease associated with aging in the human population. This disease is characterized by the following 4 structural changes : Atrophy of the Cortex, Parasympathetic, and other neural cells, the existence of Neurofibrillary tangles (NFTs), and the accumulation of Senile plaques. NFTs and Senile plaques is known to be the index of this disease. Senile plaques disturbs the neutro transmission and depletes of Acetylcholine. So, Recovery of Acetylcholine is the primal objective for treating Alzheimer's disease. So, Inhibiting the activity of Acetylcholine Esterase (AChE), which causes the hydrolysus of acetylcholine into choline and acetate, can be seen as a key role for treating Alzheimer's disease. Increasing body of evidence has been demonstrated that Bee Venom Acupuncture (BV) could compete with complex protein involving in multiple step of $NF-_{\kappa}B$ activation and exert the anti -inflammatory potential of combined inhibition of the prostanoid and nitric oxide synthesis systems by inhibition of IKK and $NF-_{\kappa}B$. The effect of BV through behavioral tests after memory impairment induced by Scopolamine. We examined the improving effect of BV on the Scopolamine (1 mg/Kg, i.p.)-induced memorial impairment using passive avoidance response and water maze tests in the mice. BV (0.84, $1.67\;{\mu}g/ml$) reversed the Scopolamine-induced memorial impairment in dose dependent manner. This study therefore suggests that BV acupuncture method may be useful for prevention of development or progression of AD.

• 대한방사성의약품학회지
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• 제9권1호
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• pp.3-8
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• 2023

Parkinson's disease is a neurodegenerative disease caused by damage to brain neurons related to dopamine. Non-clinical animal models mainly used in Parkinson's disease research include drug-induced models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine, and genetically modified transgenic animal models. Parkinson's diagnosis can be made using brain imaging of the substantia nigra-striatal dopamine system and using a radiotracer that specifically binds to the dopamine transporter. In this study, ¹⁸F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane was used to confirm the image evaluation cutoff between normal and parkinson's disease models, and to confirm model persistence over time. In addition, the efficacy of single or combined administration of clinically used therapeutic drugs in parkinson's animal models was evaluated. Image analysis was performed using the PMOD software. Converted to standardized uptake value, and analyzed by standardized uptake value ratio by dividing the average value of left striatum by the average value of right striatum obtained by applying positron emission tomography images to the atlas magnetic resonance template. The image cutoff of the normal and the parkinson's disease model was calculated as SUVR=0.829, and it was confirmed that it was maintained during the test period. In the three-drug combination administration group, the right and left striatum showed a high symmetry of more than 0.942 on average and recovered significantly. Images using ¹⁸F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane are thought to be able to diagnose and evaluate treatment efficacy of non-clinical Parkinson's disease.

• Journal of Preventive Medicine and Public Health
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• 제43권1호
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• pp.9-17
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• 2010

Objectives: Parkinson's disease is one of the most common neurodegenerative diseases in the elderly population. In order to estimate the prevalence of Parkinson's disease in the community, the application of a good screening tool is essential. We evaluated the validity and reliability of a Parkinson's disease screening questionnaire and propose an alternative measure to improve its validity for use in community surveys. Methods: We designed the study in a three-phase approach consisting of a screening questionnaire, neurologic examination, and confirmatory examination. A repeated survey was administered to patients with disease detected in the community and on 150 subjects. We examined internal consistency using Cronbach's alpha test, test-retest reliability using the kappa statistic, and validity using sensitivity, specificity, and ROC curves. Unadjusted odds ratios were utilized for the estimation of weights for each questionnaire item. Results: The Cronbach's alpha of the questionnaire was 0.708. The kappa statistic for test-retest reliability was good to generally fair in most of the items. When newly proposed weighting scores were used, the optimum cut-off value was 7/8. When cut-off value was 5/6 for surveying prevalence in a community, the sensitivity was 0.98, and the specificity was 0.61, with simultaneous improvement in reliability. Conclusions: We recommend 5/6 as the ideal cut-off value for the survey of PD prevalence in community. This questionnaire designed for the Korean community could help future epidemiologic studies of PD.

• Journal of Microbiology and Biotechnology
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• 제14권2호
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• pp.417-421
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• 2004

A normal prion protein (PrPc) is converted to a protease resistant isoform (PrPsc) by an apparent self-propagating activity in bovine spongiform encephalopathies (BSE), which is a neurodegenerative disease. The cDNA encoding bovine PrP open reading frame (ORP) in Korean cattle was cloned by polymerase chain reaction (PCR). The cloned cDNA had a length of 795 base pairs which coded for a protein of 264 amino acid residues with a calculated molecular mass of 28.6 kDa. Identities of 90, 90, 79 and 78% on nucleotide and 94, 94, 84, and 84% on amino acid sequence were shown to PrP genes from sheep, goat, human, and mouse, respectively. The cloned DNA was ligated into the pQE30 expression vector and transformed into E. coli M15. The PrP was expressed by induction with isopropyl-$\beta$-D-thiogalactoside (IPTG) and purified on the Ni-NTA affinity column. High specific activities of the recombinant PrP were observed in the fraction of pH 5.8 eluate and showed a molecular mass of-29 kDa on SDS-PAGE and Western blot analysis.

• Korean Journal of Acupuncture
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• 제26권4호
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• pp.77-88
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• 2009

Background : Qigong is an exercise therapy based on the principles of Traditional East Asian Medicine. The exercises combine the practice of motion and breathing, both guided by mental imagery. Beneficial effects of qigong have been reported on a variety of complaints in chronically ill patients and on gait imbalance in the elderly. Parkinson's disease is a progressive neurodegenerative disorder that affects neurophysiological function, movement abilities, and quality of life. Objectives : We developed a qigong program based on the Traditional East Asian medical theory regarding the improvement of clinical symptoms of Parkinson's disease. Methods and Results : Our qigong program consists of three parts. The first one includes movements which stimulate the meridians that run from the toes to the top of the head. The second one is composed of breathing and qigong movements that create harmony and balance with the circulation of Qi and blood on the Meridians. The third is a stage of finger pressure therapy and massage from Daoyin medical qigong to maintain meridian stability. Conclusions : These qigong program would help relieve the clinical symptoms of Parkinson's disease patients.

• BMB Reports
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• 제40권5호
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• pp.662-669
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• 2007

Although the function of cellular prion protein (PrP$^C$) and the pathogenesis of prion diseases have been widely described, the mechanisms are not fully clarified. In this study, increases of the portion of non-glycosylated prion protein deposited in the hamster brains infected with scrapie strain 263K were described. To elucidate the pathological role of glycosylation profile of PrP, wild type human PrP (HuPrP) and two genetic engineering generated non-glycosylated PrP mutants (N181Q/N197Q and T183A/T199A) were transiently expressed in human astrocytoma cell line SF126. The results revealed that expressions of non-glycosylated PrP induced significantly more apoptosis cells than that of wild type PrP. It illustrated that Bcl-2 proteins might be involved in the apoptosis pathway of non-glycosylated PrPs. Our data highlights that removal of glycosylation of prion protein provokes cells apoptosis.

• Biomolecules & Therapeutics
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• 제15권1호
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• pp.16-26
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• 2007

Tissue plasminogen activator (tPA) is a serine protease catalyzing the proteolytic conversion of plasminogen into plasmin, which is involved in thrombolysis. During last two decades, the role of tPA in brain physiology and pathology has been extensively investigated. tPA is expressed in brain regions such as cortex, hippocampus, amygdala and cerebellum, and major neural cell types such as neuron, astrocyte, microglia and endothelial cells express tPA in basal status. After strong neural stimulation such as seizure, tPA behaves as an immediate early gene increasing the expression level within an hour. Neural activity and/or postsynaptic stimulation increased the release of tPA from axonal terminal and presumably from dendritic compartment. Neuronal tPA regulates plastic changes in neuronal function and structure mediating key neurologic processes such as visual cortex plasticity, seizure spreading, cerebellar motor learning, long term potentiation and addictive or withdrawal behavior after morphine discontinuance. In addition to these physiological roles, tPA mediates excitotoxicity leading to the neurodegeneration in several pathological conditions including ischemic stroke. Increasing amount of evidence also suggest the role of tPA in neurodegenerative diseases such as Alzheimer's disease and multiple sclerosis even though beneficial effects was also reported in case of Alzheimer's disease based on the observation of tPA-induced degradation of $A{\beta}$ aggregates. Target proteins of tPA action include extracellular matrix protein laminin, proteoglycans and NMDA receptor. In addition, several receptors (or binding partners) for tPA has been reported such as low-density lipoprotein receptor-related protein (LRP) and annexin II, even though intracellular signaling mechanism underlying tPA action is not clear yet. Interestingly, the action of tPA comprises both proteolytic and non-proteolytic mechanism. In case of microglial activation, tPA showed non-proteolytic cytokine-like function. The search for exact target proteins and receptor molecules for tPA along with the identification of the mechanism regulating tPA expression and release in the nervous system will enable us to better understand several key neurological processes like teaming and memory as well as to obtain therapeutic tools against neurodegenerative diseases.

• Journal of Ginseng Research
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• 제45권2호
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• pp.325-333
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• 2021

Background: Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders. Enhancing hippocampal neurogenesis by promoting proliferation and differentiation of neural stem cells (NSCs) is a promising therapeutic strategy for AD. 20(S)-protopanaxadiol (PPD) and oleanolic acid (OA) are small, bioactive compounds found in ginseng that can promote NSC proliferation and neural differentiation in vitro. However, it is currently unknown whether PPD or OA can attenuate cognitive deficits by enhancing hippocampal neurogenesis in vivo in a transgenic APP/PS1 AD mouse model. Here, we administered PPD or OA to APP/PS1 mice and monitored the effects on cognition and hippocampal neurogenesis. Methods: We used the Morris water maze, Y maze, and open field tests to compare the cognitive capacities of treated and untreated APP/PS1 mice. We investigated hippocampal neurogenesis using Nissl staining and BrdU/NeuN double labeling. NSC proliferation was quantified by Sox2 labeling of the hippocampal dentate gyrus. We used western blotting to determine the effects of PPD and OA on Wnt/GSK3β/β-catenin pathway activation in the hippocampus. Results: Both PPD and OA significantly ameliorated the cognitive impairments observed in untreated APP/PS1 mice. Furthermore, PPD and OA significantly promoted hippocampal neurogenesis and NSC proliferation. At the mechanistic level, PPD and OA treatments resulted in Wnt/GSK-3β/β-catenin pathway activation in the hippocampus. Conclusion: PPD and OA ameliorate cognitive deficits in APP/PS1 mice by enhancing hippocampal neurogenesis, achieved by stimulating the Wnt/GSK-3β/β-catenin pathway. As such, PPD and OA are promising novel therapeutic agents for the treatment of AD and other neurodegenerative diseases.