• 제목/요약/키워드: Neurodegenerative disorders

검색결과 240건 처리시간 0.021초

Fishing for synucleinopathy models

  • Noor, Suzita Mohd;Norazit, Anwar
    • Fisheries and Aquatic Sciences
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    • 제25권3호
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    • pp.117-139
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    • 2022
  • Synucleinopathies such as Parkinson's disease (PD) are incurable neurodegenerative conditions characterised by the abnormal aggregation of α-synuclein protein in neuronal cells. In PD, fibrillary synuclein aggregation forms Lewy bodies and Lewy neurites in the substantia nigra and cortex on the brain. Dementia with Lewy bodies and multiple system atrophy are also associated with α-synuclein protein abnormalities. α-synuclein is one of three synuclein proteins, and while its precise function is still unknown, one hypothesis posits that α-synuclein propagates from the enteric nervous system through the vagus nerve and into the brain, resulting in synucleinopathy. Studies on synucleinopathies should thus encompass not only the central nervous system but must necessarily include the gut and microbiome. The zebrafish (Danio rerio) is a well-established model for human neuronal pathologies and have been used in studies ranging from genetic models of hereditary disorders to neurotoxin-induced neurodegeneration as well as gut-brain-axis studies. There is significant genetic homology between zebrafish and mammalian vertebrates which is what makes the zebrafish so amenable to modelling human conditions but in the case of synucleinopathies, the zebrafish notably does not possess an α-synuclein homolog. Synuclein orthologs are present in the zebrafish however, and transgenic zebrafish that carry human α-synuclein have been generated. In addition, the zebrafish is a highly advantageous model and ideal replacement for reducing the use of mammalian models. This review discusses the application of the zebrafish as a model for synucleinopathies in efforts to further understand synuclein function and explore therapeutic strategies.

Potential role of phytochemicals in brain plasticity: Focus on polyunsaturated fatty acids

  • Yook, Jang Soo;Lee, Minchul
    • Korean Journal of Exercise Nutrition
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    • 제24권1호
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    • pp.14-18
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    • 2020
  • [Purpose] Functional foods are thought to strongly influence the structure and function of the brain. Previous studies have reported that brain-boosting diets may enhance neuroprotective functions. Certain foods are particularly rich in nutrients like phytochemicals that are known to support brain plasticity; such foods are commonly referred to as brain foods. [Methods] In this review, we briefly explore the scientific evidence supporting the neuroprotective activity of a number of phytochemicals with a focus on phenols and polyunsaturated fatty acids such as flavonoid, olive oil, and omega-3 fatty acid. [Results] The aim of this study was to systematically examine the primary issues related to phytochemicals in the brain. These include (a) the brain-gut-microbiome axis; (b) the effects of phytochemicals on gut microbiome and their potential role in brain plasticity; (c) the role of polyunsaturated fatty acids in brain health; and (d) the effects of nutrition and exercise on brain function. [Conclusion] This review provides evidence supporting the view that phytochemicals from medicinal plants play a vital role in maintaining brain plasticity by influencing the brain-gut-microbiome axis. The consumption of brain foods may have neuroprotective effects, thus protecting against neurodegenerative disorders and promoting brain health.

Neuroprotective Activity of Boesenbergia rotunda Against Glutamate Induced Oxidative Stress in HT22 Cells (글루타메이트에 의해 산화적 스트레스를 받은 HT22 세포에서 핑거루트의 신경세포 보호활성)

  • Kim, Eun Seo;Ma, Choong Je
    • Korean Journal of Pharmacognosy
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    • 제53권2호
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    • pp.79-86
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    • 2022
  • Excessive glutamate causes oxidative stress in neuronal cells, which can cause degenerative neurological disorders. We tried to find medicinal plant showed neuroprotective activity by using glutamate-injured HT22 cell as a model system. In this study, we found that Boesenbergia rotunda methanol extract showed neuroprotective activity against glutamate induced neurotoxicity in mouse hippocampal HT22 cells. B. rotunda methanol extract suppressed the formation of reactive oxygen species and decreased intracellular Ca2+concentration. Also, B. rotunda made mitochondrial membrane potential maintain to normal levels. In addition, B. rotunda increased total glutathione amount and activated antioxidative enzyme such as glutathione reductase and glutathione peroxidase compared to glutamate-treated groups. These results suggested that B. rotunda decreased neuronal cell death damaged by high concentrations of glutamate treatment, via antioxidative mechanism and might be one of candidate of development of new drug to treat neurodegenerative disease such as Alzheimer's disease.

The Anti-inflammatory Mechanism of Pu-erh Tea via Suppression the Activation of NF-κB/HIF-1α in LPS-stimulated RAW264.7 Cells

  • Su-Jin Kim
    • Biomedical Science Letters
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    • 제29권2호
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    • pp.58-65
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    • 2023
  • Pu-erh tea, a popular and traditional Chinese tea, possesses various health-promoting effects, including inhibiting tumor cell progression and preventing type II diabetes and neurodegenerative disorders. However, the precise anti-inflammatory mechanisms are not well understood. In present study, we elucidated the anti-inflammatory mechanism of Pu-erh tea in lipopolysaccharide (LPS)-activated RAW264.7 cells. We explored the effects of Pu-erh tea on the levels of inflammatory-related genes, including inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and prostaglandin E2 (PGE2) in LPS-activated RAW264.7 cells. Moreover, we investigated its regulatory effects on nuclear factor-kappa B (NF)-κB and hypoxia-inducible-factor (HIF)-1α activation. The findings of this study demonstrated that Pu-erh tea inhibited the LPS-increased inflammatory cytokines and PGE2 release, as well as COX-2 and iNOS expression. Moreover, we confirmed that the anti-inflammatory mechanism of Pu-erh tea occurs via the inhibition of NF-κB and HIF-1α activation. Conclusively, these findings provide experimental evidence that Pu-erh tea may be useful candidate in the treatment of inflammatory-related diseases.

Protective Effects of Lacticaseibacillus rhamnosus IDCC3201 on Motor Functions and Anxiety Levels in a Chronic Stress Mouse Model

  • Jae Gwang Song;Daye Mun;Bomi Lee;Minho Song;Sangnam Oh;Jun-Mo Kim;Jungwoo Yang;Younghoon Kim;Hyung Wook Kim
    • Food Science of Animal Resources
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    • 제43권6호
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    • pp.1044-1054
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    • 2023
  • Growing evidence indicates a crucial role of the gut microbiota in physiological functions. Gut-brain axis imbalance has also been associated with neuropsychiatric and neurodegenerative disorders. Studies have suggested that probiotics regulate the stress response and alleviate mood-related symptoms. In this study, we investigated the effects of the probiotic Lacticaseibacillus rhamnosus IDCC3201 (L3201) on the behavioral response and fecal metabolite content in an unpredictable chronic mild stress (UCMS) mouse model. Our study shows that chronic stress in mice for three weeks resulted in significant changes in behavior, including lower locomotor activity, higher levels of anxiety, and depressive-like symptoms, compared to the control group. Metabolomic analysis demonstrated that disrupted fecal metabolites associated with aminoacyl-tRNA biosynthesis and valine, leucine, and isoleucine biosynthesis by UCMS were restored with the administration of L3201. Oral administration of the L3201 ameliorated the observed changes and improved the behavioral alterations along with fecal metabolites, suggesting that probiotics play a neuroprotective role.

Impaired Autophagic Flux in Glucose-Deprived Cells: An Outcome of Lysosomal Acidification Failure Exacerbated by Mitophagy Dysfunction

  • Eun Seong Hwang;Seon Beom Song
    • Molecules and Cells
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    • 제46권11호
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    • pp.655-663
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    • 2023
  • Autophagy dysfunction is associated with human diseases and conditions including neurodegenerative diseases, metabolic issues, and chronic infections. Additionally, the decline in autophagic activity contributes to tissue and organ dysfunction and aging-related diseases. Several factors, such as down-regulation of autophagy components and activators, oxidative damage, microinflammation, and impaired autophagy flux, are linked to autophagy decline. An autophagy flux impairment (AFI) has been implicated in neurological disorders and in certain other pathological conditions. Here, to enhance our understanding of AFI, we conducted a comprehensive literature review of findings derived from two well-studied cellular stress models: glucose deprivation and replicative senescence. Glucose deprivation is a condition in which cells heavily rely on oxidative phosphorylation for ATP generation. Autophagy is activated, but its flux is hindered at the autolysis step, primarily due to an impairment of lysosomal acidity. Cells undergoing replicative senescence also experience AFI, which is also known to be caused by lysosomal acidity failure. Both glucose deprivation and replicative senescence elevate levels of reactive oxygen species (ROS), affecting lysosomal acidification. Mitochondrial alterations play a crucial role in elevating ROS generation and reducing lysosomal acidity, highlighting their association with autophagy dysfunction and disease conditions. This paper delves into the underlying molecular and cellular pathways of AFI in glucose-deprived cells, providing insights into potential strategies for managing AFI that is driven by lysosomal acidity failure. Furthermore, the investigation on the roles of mitochondrial dysfunction sheds light on the potential effectiveness of modulating mitochondrial function to overcome AFI, offering new possibilities for therapeutic interventions.

Development and Validation of a Screening Questionnaire for Dementia With Lewy Bodies (DLB): the DLB Screening Questionnaire (DLBSQ)

  • Mincheol Park;Kyoungwon Baik;Young H. Sohn;Byoung Seok Ye
    • Dementia and Neurocognitive Disorders
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    • 제23권1호
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    • pp.11-21
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    • 2024
  • Background and Purpose: Although dementia with Lewy bodies (DLB) is the second most common cause of neurodegenerative dementia, its clinical prevalence is low. We developed a short and easy-to-complete DLB screening questionnaire (DLBSQ) to raise diagnostic sensitivity in routine clinical settings. Methods: A total of 501 participants were retrospectively enrolled, including 71 controls, 184 patients without DLB, and 246 patients with probable DLB. All patients underwent clinical evaluation, including core features of DLB, the DLBSQ, brain magnetic resonance imaging, and detailed neuropsychological assessments. The diagnostic performance of the DLBSQ for probable DLB was investigated using a receiver operating characteristic curve analysis. Results: Total DLBSQ score was associated with visuospatial and frontal/executive dysfunction and the diagnosis of probable DLB. The area under the receiver operating characteristic curve for total DLBSQ score was 0.727. Youden's method revealed an optimal cutoff value of 3. The sensitivity and specificity of the DLBSQ were 68.7% and 62.4%, respectively. Its discriminating performance improved when cognitive test profiles were additionally considered (area under the curve: 0.822, sensitivity: 80.6%, and specificity: 70.4%). Conclusions: The DLBSQ might be a useful screening tool for DLB in routine clinical practice with good sensitivity and specificity.

Anti-neuroinflammatory Effects of a Locusta migratoria Ethanol Extract in LPS-stimulated BV-2 Microglia (LPS로 자극된 미세아교세포에서 풀무치 에탄올 추출물의 신경염증 억제 효능)

  • Lee, Hwa Jeong;Seo, Minchul;Lee, Joon Ha;Kim, In-Woo;Kim, Sun Young;Hwang, Jae-Sam;Kim, Mi-Ae
    • Journal of Life Science
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    • 제28권11호
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    • pp.1332-1338
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    • 2018
  • Activated microglia, induced by various pathogens, protect neurons and maintain homeostasis of the central nervous system (CNS). However, severe activation causes neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease because of the secretion of various neurotoxic molecules, such as nitric oxide (NO), prostaglandin (PG), and pro-inflammatory cytokines. Because chronic microglial activation endangers neuronal survival, negative regulators of microglial activation have been identified as potential therapeutic candidates for treatment of many neurological diseases. One potential source of these regulators is Locusta migratoria, a grasshopper of the Acrididae, usually 4-6 cm in size, belonging to the family of large insects in Acrididae. This grasshopper is an edible insect resource that can be consumed by humans as protein source or used for animal feed. The aim of the present study was to examine the inhibitory effects of a L. migratoria ethanol extract (LME) on the production of inflammatory mediators in LPS-stimulated BV-2 microglia cells. The extract significantly inhibited the NO, iNOS, COX-2, and pro-inflammatory cytokine ($TNF-{\alpha}$, IL-6 and $IL-1{\beta}$) levels in BV-2 microglia cell. Because the inhibition of microglial activation may be an effective solution for treating brain disorders like Alzheimer's and Parkinson's diseases, these results suggest that LME may be a potential therapeutic agent for the treatment of brain disorders induced by neuroinflammation.

A Case of Multiple System Atrophy with Antecollis and Gait Disturbance Treated with Korean Medicine (경전굴 및 보행장애를 주소로 하는 다계통 위축증 환자의 한의 치료 증례 1례)

  • Kim, Seo-young;Choi, Jeong-woo;Jeong, Hye-seon;Lee, Sang-hwa;Yang, Seung-bo;Cho, Seung-yeon;Park, Jung-mi;Ko, Chang-nam;Park, Seong-uk
    • The Journal of Internal Korean Medicine
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    • 제40권5호
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    • pp.851-864
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    • 2019
  • Multiple system atrophy is a neurodegenerative disease that causes diverse bodily dysfunctions (cerebellar, pyramidal, automatic, and urological, in any combination), as well as Parkinsonism. Patients with multiple system atrophy commonly display antecollis, a condition where the patient's head tilts forward more than 45 degrees. Despite its common occurrence in these patients, no current standardized therapies are effective for treating antecollis. In this study, Korean medicinal treatments, including Chuna manual therapy, pharmaco-acupuncture, bee venom acupuncture, acupuncture, herbal medicine, and moxibustion therapy, were administered to the patient over a 27-day period. After the treatment, assessments of the head position on the EPIS-PD scale (Part I) and at a standing position from the side (Part II) both revealed improvements. As the head flexion angle decreased, the patient's head posture improved, as determined by a decrease in angle from 80 degrees to 30 degrees in the upright, standing position. As a result, patients who previously were unable to walk without the support of walking frames could now roam freely and independently, with significant increases in both walking speed and distance. In essence, this study suggests that Korean medicine is an effective treatment for patients with multiple system atrophy who suffer from antecollis and gait disorders.

Phosphodiesterase-5 Inhibitor Attenuates Anxious Phenotypes and Movement Disorder Induced by Mild Ischemic Stroke in Rats

  • Yu, Yeon Hee;Kim, Seong-Wook;Kang, Juhyeon;Song, Yejin;Im, yHyuna;Kim, Seo Jeong;Yoo, Dae Young;Lee, Man-Ryul;Park, Dae-Kyoon;Oh, Jae Sang;Kim, Duk-Soo
    • Journal of Korean Neurosurgical Society
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    • 제65권5호
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    • pp.665-679
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    • 2022
  • Objective : Patients with mild ischemic stroke experience various sequela and residual symptoms, such as anxious behavior and deficits in movement. Few approaches have been proved to be effective and safe therapeutic approaches for patients with mild ischemic stroke by acute stroke. Sildenafil (SIL), a phosphodiesterase-5 inhibitor (PDE5i), is a known remedy for neurodegenerative disorders and vascular dementia through its angiogenesis and neurogenesis effects. In this study, we investigated the efficacy of PDE5i in the emotional and behavioral abnormalities in rats with mild ischemic stroke. Methods : We divided the rats into four groups as follows (n=20, respectively) : group 1, naïve; group 2, middle cerebral artery occlusion (MCAo30); group 3, MCAo30+SIL-pre; and group 4, MCAo30+SIL-post. In the case of drug administration groups, single dose of PDE5i (sildenafil citrate, 20 mg/kg) was given at 30-minute before and after reperfusion of MCAo in rats. After surgery, we investigated and confirmed the therapeutic effect of sildenafil on histology, immunofluorescence, behavioral assays and neural oscillations. Results : Sildenafil alleviated a neuronal loss and reduced the infarction volume. And results of behavior task and immunofluorescence shown possibility that anti-inflammation process and improve motor deficits sildenafil treatment after mild ischemic stroke. Furthermore, sildenafil treatment attenuated the alteration of theta-frequency rhythm in the CA1 region of the hippocampus, a known neural oscillatory marker for anxiety disorder in rodents, induced by mild ischemic stroke. Conclusion : PDE5i as effective therapeutic agents for anxiety and movement disorders and provide robust preclinical evidence to support the development and use of PDE5i for the treatment of mild ischemic stroke residual disorders.