• 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.

• Nuclear Medicine and Molecular Imaging
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• 제42권sup1호
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• pp.177-180
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• 2008

Parkinson's disease is the second most common neurodegenerative disorder. It is slowly progressive disease that affects a small area of cells in the mid brain known as the substantia nigra. Gradual degeneration of these cells causes a reduction in a vital chemical known as dopamine. In the diagnosis of Parkinson's disease, it has difficulty in biopsy and limits in radiologic modalities. $^{18}F-FDG$ PET shows various findings from normal to diffuse decrement of FDG uptake. $^{18}F-FDG$ PET is expected to be a evaluation tool in the treatment of Parkinson's disease.

• 대한한방내과학회지
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• 제19권1호
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• pp.291-300
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• 1998

Dementia is the neurodegenerative process that affects cognition, behavior and function and one of the most prominent diseases of dementia is Alzheimer's disease(AD). AD is a dementing illness characterized clinically by the progressive and irreversible deafferentation of the limbic system, association neocortex and basal forebrain. A number of conditions are known to be predisposing risk factors for AD. In several of these, initiation of glial-mediated inflammatory pathways as a mechanism of AD is getting a lot of attention. On the other hand, a biochemical marker for monitoring the onset and progression of the disease would be a valuable tool for disease management. Also such a marker might be used as an end point in clinical intervention protocols. This biochemical marker will have the potential for identifying subjects afflicted with the disease and possibly for monitoring the onset and longitudinal progression of the disease. Here we have reviewed the latest papers of different approaches to AD. Of course, there is a section of PET which is very useful clinically nowadays.

• 대한핵의학회지
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• 제37권1호
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• pp.13-23
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• 2003

Neurodegenerative disorders cause a variety of dementia including Alzheimer disease, frontotemporal dementia, dementia with Lewy bodies, corticobasal degeneration, progressive supranuclear palsy, and Huntington's disease. PET scan is useful for early detection and differential diagnosis of these dementing disorders. Also, it provides valuable information about clinico-anatomical correlation, allowing better understanding of function of brain. Here we discuss recent achievements PET studies regarding these dementing disorders. Future progress in PET technology, new tracers, and image analysis will play an important role in further clarifying the disease pathophysiology and brain functions.

• Journal of Genetic Medicine
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• 제18권1호
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• pp.16-23
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• 2021

GLB1-related disorders comprise two phenotypically unique disorders: GM1 gangliosidosis and Morquio B disease. These autosomal recessive disorders are caused by b-galactosidase deficiency. A hallmark of GM1 gangliosidosis is central nervous system degeneration where ganglioside synthesis is highest. The accumulation of keratan sulfate is the suspected cause of the bone findings in Morquio B disease. GM1 gangliosidosis is clinically characterized by a neurodegenerative disorder associated with dysostosis multiplex, while Morquio B disease is characterized by severe skeletal manifestations and the preservation of intelligence. Morquio B disease and GM1 gangliosidosis may be on a continuum of skeletal involvement. There is currently no effective treatment for GLB1-related disorders. Recently, multiple interventions have been developed and there are several ongoing clinical trials.

• BMB Reports
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• 제56권12호
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• pp.657-662
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• 2023

Neurodegenerative diseases are characterized by distinct protein aggregates, such as those of α-synuclein and tau. Lysosomal defect is a key contributor to the accumulation and propagation of aberrant protein aggregates in these diseases. The discoveries of common proteinopathies in multiple forms of lysosomal storage diseases (LSDs) and the identification of some LSD genes as susceptible genes for those proteinopathies suggest causative links between LSDs and the proteinopathies. The present study hypothesized that defects in lysosomal genes will differentially affect the propagation of α-synuclein and tau proteins, thereby determining the progression of a specific proteinopathy. We established an imaging-based high-contents screening (HCS) system in Caenorhabditis elegans (C. elegans) model, by which the propagation of α-synuclein or tau is measured by fluorescence intensity. Using this system, we performed RNA interference (RNAi) screening to induce a wide range of lysosomal malfunction through knock down of 79 LSD genes, and to obtain the candidate genes with significant change in protein propagation. While some LSD genes commonly affected both α-synuclein and tau propagation, our study identified the distinct sets of LSD genes that differentially regulate the propagation of either α-synuclein or tau. The specificity and efficacy of these LSD genes were retained in the disease-related phenotypes, such as pharyngeal pumping behavior and life span. This study suggests that distinct lysosomal genes differentially regulate the propagation of α-synuclein and tau, and offer a steppingstone to understanding disease specificity.

• Bulletin of the Korean Chemical Society
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• 제34권2호
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• pp.406-410
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• 2013

Tetrahyropapaveroline (THP) is compound derived from dopamine metabolism and is capable of causing dopaminergic neurodegenerative disorder, such as Parkinson's disease (PD). The aim of this study was to evaluate the potential of THP to cause oxidative damage on the structure of cytochrome c (cyt c). Our data showed that THP led to protein aggregation and the formation of carbonyl compound in protein aggregates. THP also induced the release of iron from cyt c. Reactive oxygen species (ROS) scavengers and iron specific chelator inhibited the THP-mediated cyt c modification and carbonyl compound formation. The results of this study show that ROS may play a critical role in THP-induced cyt c modification and iron releasing of cyt c. When cyt c that has been exposed to THP was subsequently analyzed by amino acid analysis, lysine, histidine and methionine residues were particularly sensitive. It is suggested that oxidative damage of cyt c by THP might induce the increase of iron content in cells and subsequently led to the deleterious condition. This mechanism is associated with the deterioration of organs under neurodegenerative disorder such as PD.

• Molecules and Cells
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• 제41권12호
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• pp.1000-1007
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• 2018

Mitochondria and endoplasmic reticulum (ER) are essential organelles in eukaryotic cells, which play key roles in various biological pathways. Mitochondria are responsible for ATP production, maintenance of $Ca^{2+}$ homeostasis and regulation of apoptosis, while ER is involved in protein folding, lipid metabolism as well as $Ca^{2+}$ homeostasis. These organelles have their own functions, but they also communicate via mitochondrial-associated ER membrane (MAM) to provide another level of regulations in energy production, lipid process, $Ca^{2+}$ buffering, and apoptosis. Hence, defects in MAM alter cell survival and death. Here, we review components forming the molecular junctions of MAM and how MAM regulates cellular functions. Furthermore, we discuss the effects of impaired ER-mitochondrial communication in various neurodegenerative diseases.

• Molecules and Cells
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• 제47권1호
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• pp.100006.1-100006.10
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• 2024

Nitric oxide (NO) serves as an evolutionarily conserved signaling molecule that plays an important role in a wide variety of cellular processes. Extensive studies in Drosophila melanogaster have revealed that NO signaling is required for development, physiology, and stress responses in many different types of cells. In neuronal cells, multiple NO signaling pathways appear to operate in different combinations to regulate learning and memory formation, synaptic transmission, selective synaptic connections, axon degeneration, and axon regrowth. During organ development, elevated NO signaling suppresses cell cycle progression, whereas downregulated NO leads to an increase in larval body size via modulation of hormone signaling. The most striking feature of the Drosophila NO synthase is that various stressors, such as neuropeptides, aberrant proteins, hypoxia, bacterial infection, and mechanical injury, can activate Drosophila NO synthase, initially regulating cellular physiology to enable cells to survive. However, under severe stress or pathophysiological conditions, high levels of NO promote regulated cell death and the development of neurodegenerative diseases. In this review, I highlight and discuss the current understanding of molecular mechanisms by which NO signaling regulates distinct cellular functions and behaviors.

• BMB Reports
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• 제49권6호
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• pp.337-343
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• 2016

Understanding of trafficking, processing, and degradation mechanisms of amyloid precursor protein (APP) is important because APP can be processed to produce β-amyloid (Aβ), a key pathogenic molecule in Alzheimer's disease (AD). Here, we found that APP contains KFERQ motif at its C-terminus, a consensus sequence for chaperone-mediated autophagy (CMA) or microautophagy which are another types of autophagy for degradation of pathogenic molecules in neurodegenerative diseases. Deletion of KFERQ in APP increased C-terminal fragments (CTFs) and secreted N-terminal fragments of APP and kept it away from lysosomes. KFERQ deletion did not abolish the interaction of APP or its cleaved products with heat shock cognate protein 70 (Hsc70), a protein necessary for CMA or microautophagy. These findings suggest that KFERQ motif is important for normal processing and degradation of APP to preclude the accumulation of APP-CTFs although it may not be important for CMA or microautophagy.