• Title/Summary/Keyword: Neurodegenerative disease

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Phagocytic Roles of Glial Cells in Healthy and Diseased Brains

  • Jung, Yeon-Joo;Chung, Won-Suk
    • Biomolecules & Therapeutics
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    • v.26 no.4
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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.

Immune inflammatory modulation as a potential therapeutic strategy of stem cell therapy for ALS and neurodegenerative diseases

  • Kim, Seung Hyun;Oh, Ki-Wook;Jin, Hee Kyung;Bae, Jae-Sung
    • BMB Reports
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    • v.51 no.11
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    • pp.545-546
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    • 2018
  • With emerging evidence on the importance of non-cell autonomous toxicity in neurodegenerative diseases, therapeutic strategies targeting modulation of key immune cells. including microglia and Treg cells, have been designed for treatment of ALS and other neurodegenerative diseases. Strategy switching the patient's environment from a pro-inflammatory toxic to an anti-inflammatory, and neuroprotective condition, could be potential therapy for neurodegenerative diseases. Mesenchymal stem cells (MSCs) regulate innate and adaptive immune cells, through release of soluble factors such as $TGF-{\beta}$ and elevation of regulatory T cells (Tregs) and T helper-2 cells (Th2 cells), would play important roles, in the neuroprotective effect on motor neuronal cell death mechanisms in ALS. Single cycle of repeated intrathecal injections of BM-MSCs demonstrated a clinical benefit lasting at least 6 months, with safety, in ALS patients. Cytokine profiles of CSF provided evidence that BM-MSCs, have a role in switching from pro-inflammatory to anti-inflammatory conditions. Inverse correlation of $TGF-{\beta}1$ and MCP-1 levels, could be a potential biomarker to responsiveness. Thus, additional cycles of BM-MSC treatment are required, to confirm long-term efficacy and safety.

Neuroprotective effects of hesperetin on H2O2-induced damage in neuroblastoma SH-SY5Y cells

  • Ha-Rin Moon;Jung-Mi Yun
    • Nutrition Research and Practice
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    • v.17 no.5
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    • pp.899-916
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    • 2023
  • BACKGROUND/OBJECTIVES: Oxidative stress is a fundamental neurodegenerative disease trigger that damages and decimates nerve cells. Neurodegenerative diseases are chronic central nervous system disorders that progress and result from neuronal degradation and loss. Recent studies have extensively focused on neurodegenerative disease treatment and prevention using dietary compounds. Heseperetin is an aglycone hesperidin form with various physiological activities, such as anti-inflammation, antioxidant, and antitumor. However, few studies have considered hesperetin's neuroprotective effects and mechanisms; thus, our study investigated this in hydrogen peroxide (H2O2)-treated SH-SY5Y cells. MATERIALS/METHODS: SH-SY5Y cells were treated with H2O2 (400 µM) in hesperetin absence or presence (10-40 µM) for 24 h. Three-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assays detected cell viability, and 4',6-diamidino-2-phenylindole staining allowed us to observe nuclear morphology changes such as chromatin condensation and apoptotic nuclei. Reactive oxygen species (ROS) detection assays measured intracellular ROS production; Griess reaction assays assessed nitric oxide (NO) production. Western blotting and quantitative polymerase chain reactions quantified corresponding mRNA and proteins. RESULTS: Subsequent experiments utilized various non-toxic hesperetin concentrations, establishing that hesperetin notably decreased intracellular ROS and NO production in H2O2-treated SH-SY5Y cells (P < 0.05). Furthermore, hesperetin inhibited H2O2-induced inflammation-related gene expression, including interluekin-6, tumor necrosis factor-α, and nuclear factor kappa B (NF-κB) p65 activation. In addition, hesperetin inhibited NF-κB translocation into H2O2-treated SH-SY5Y cell nuclei and suppressed mitogen-activated protein kinase protein expression, an essential apoptotic cell death regulator. Various apoptosis hallmarks, including shrinkage and nuclear condensation in H2O2-treated cells, were suppressed dose-dependently. Additionally, hesperetin treatment down-regulated Bax/Bcl-2 expression ratios and activated AMP-activated protein kinase-mammalian target of rapamycin autophagy pathways. CONCLUSION: These results substantiate that hesperetin activates autophagy and inhibits apoptosis and inflammation. Hesperetin is a potentially potent dietary agent that reduces neurodegenerative disease onset, progression, and prevention.

Neuroprotective Effects of Methanol Extracts of Jeju Native Plants on Hydrogen Peroxide-induced Cytotoxicity in SH-SY5Y Human Neuroblastoma Cells

  • Kong, Pil-Jae;Kim, Yu-Mi;Lee, Hee-Jae;Kim, Sung-Soo;Yoo, Eun-Sook;Chun, Wan-Joo
    • The Korean Journal of Physiology and Pharmacology
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    • v.11 no.5
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    • pp.171-174
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    • 2007
  • Neuronal death is a common characteristic hallmark of a variety of neurodegenerative disorders including Alzheimer's disease and Parkinson's disease. However, there have been no effective drugs to successfully prevent neuronal death in those diseases, whereas oriental medicinal plants have to possess valuable therapeutic potentials to treat neurodegenerative diseases. In the present study, in an attempt to provide neuroprotective agents from natural plants, 80% methanol extracts of a wide range of medicinal plants, which are native to Jeju Island in Korea, were prepared and their protective effects on hydrogen peroxide-induced apoptotic cell death were examined. Among those tested, extracts from Smilax china and Saururus chinesis significantly decreased hydrogen peroxide-induced apoptotic cell death. The extracts attenuated hydrogen peroxide($H_2O_2$)-induced caspase-3 activation in a dose-dependent manner. Further, plant extracts restored $H_2O_2$-induced depletion of intracellular glutathione, a major endogenous antioxidant. The data suggest that Jeju native medicinal plants could potentially be used as therapeutic agents for treating or preventing neurodegenerative diseases in which oxidative stress is implicated.

Neuroprotective Effect of a Novel Herbmedicine, Hepad on SH-SY5Y Cells

  • Kim, Eun Hye;Park, Byung-Jun;Kim, Jung Seok;Kim, Dong-Hee;Choi, Hak Joo;Kim, In Sik
    • Biomedical Science Letters
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    • v.19 no.1
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    • pp.79-82
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    • 2013
  • Parkinson's disease is a neurodegenerative disease with a wide range of dopaminergic neuron cell death in the substantia nigra. Oxidative stress and neural degeneration are suggested to be involved in the pathogenesis of Parkinson's disease. In this study, we investigated whether a novel herbmedicine, Hepad protects against 1-methyl-4-phenylpyridnium [MPP(+)]-induced dopaminergic neurotoxicity in SH-SY5Y cells. We found that pretreatment with Hepad significantly increases the proliferation of SH-SY5Y cells (P<0.05) and reversed the loss of cell viability induced by $MPP^+$. Hepad may be a promising neuroprotective agent for the treatment of neurodegenerative disorders such as Parkinson's disease.

Mitochondrial dysfunction and Alzheimer's disease: prospects for therapeutic intervention

  • Lim, Ji Woong;Lee, Jiyoun;Pae, Ae Nim
    • BMB Reports
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    • v.53 no.1
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    • pp.47-55
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    • 2020
  • Alzheimer's disease (AD) is a multifactorial neurodegenerative disease and has become a major socioeconomic issue in many developed countries. Currently available therapeutic agents for AD provide only symptomatic treatments, mainly because the complete mechanism of the AD pathogenesis is still unclear. Although several different hypotheses have been proposed, mitochondrial dysfunction has gathered interest because of its profound effect on brain bioenergetics and neuronal survival in the pathophysiology of AD. Various therapeutic agents targeting the mitochondrial pathways associated with AD have been developed over the past decade. Although most of these agents are still early in the clinical development process, they are used to restore mitochondrial function, which provides an alternative therapeutic strategy that is likely to slow the progression of the disease. In this mini review, we will survey the AD-related mitochondrial pathways and their small-molecule modulators that have therapeutic potential. We will focus on recently reported examples, and also overview the current challenges and future perspectives of ongoing research.

The phenomenology of pain in Parkinson's disease

  • Camacho-Conde, Jose Antonio;Campos-Arillo, Victor Manuel
    • The Korean Journal of Pain
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    • v.33 no.1
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    • pp.90-96
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    • 2020
  • Background: Parkinson's disease (PD) is a neurodegenerative disorder that is the second most common disorder after Alzheimer's disease. PD includes both "motor" and "non-motor" symptoms, one of which is pain. The aim of this study was to investigate the clinical characteristics of pain in patients with PD. Methods: This cross-sectional study included 250 patients diagnosed with PD, 70% of which had mild to moderate PD (stages 2/3 of Hoehn and Yahr scale). The average age was 67.4 years, and the average duration since PD diagnosis was 7.1 years. Relevant data collected from PD patients were obtained from their personal medical history. Results: The prevalence of pain was found to be high (82%), with most patients (79.2%) relating their pain to PD. Disease duration was correlated with the frequency of intense pain (R: 0.393; P < 0.05). PD pain is most frequently perceived as an electrical current (64%), and two pain varieties were most prevalent (2.60 ± 0.63). Our findings confirm links between pain, its evolution over time, its multi-modal character, the wide variety of symptoms of PD, and the female sex. Conclusions: Our results demonstrated that the pain felt by PD patients is mainly felt as an electrical current, which contrasts with other studies where the pain is described as burning and itching. Our classification is innovative because it is based on anatomy, whereas those of other authors were based on syndromes.

Neurodegenerative Dementias: A Brief Review

  • Sin, Mo-Kyung;Khemani, Pravin
    • Journal of Korean Biological Nursing Science
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    • v.22 no.3
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    • pp.172-175
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    • 2020
  • Purpose: The purpose of this paper is to provide nurses with a concise review on neurodegenrative dementias. This review includes pathophysiology, clinical course, and tips on management of dementias from Alzheimer's disease (AD), Parkinson disease (PD) and lewy body dementia (LBD). Considering increasing numbers of dementia cases among older adults, nurses who are cognizant about dementia care are instrumental in maximizing daily activities and quality of life of patients with cognitive impairment and dementia.

Adult Neurogenesis in Insulted Brain

  • Kim, Byung-Woo;Son, Hyeon
    • Toxicological Research
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    • v.23 no.2
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    • pp.107-114
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    • 2007
  • Although there are some questions about the venues of adult neurogenesis, it is undoubtedly accepted that new neurons are born in adult brains. Adult neurogenesis is regulated by a wide array of factors. Insults harmful to brain, such as neurodegenerative diseases, seizure, ischemia and exposure to drugs of abuse, are intricately related to adult neurogenesis. Whereas neurodegenerative diseases are characterized by death or functional loss of specific neurons, recent studies report that they can be accompanied by neurogenesis. In addition, alcohol and drugs of abuse which have been reputed to cause irreversible damage to brain can also generate newly born cells in adult brain. As yet, however, we have little knowledge of the functional significance and roles of adult neurogenesis under pathological settings, not to mention under physiological settings. Accordingly, in this review we briefly summarize the results of studies which focus on adult neurogenesis in insulted brain, instead of trying to draw hurried conclusion regarding the relationship between adult neurogenesis and brain insults.