• Molecular & Cellular Toxicology
• /
• 제3권2호
• /
• pp.77-84
• /
• 2007

Millions of individuals worldwide are currently afflicted with neurodegenerative disorders such as Parkinson's disease and multiple sclerosis which are caused by the death of specific types of specialized cells in the Central Nervous System (CNS). Recently, Neural Stem Cells (NSCs) are able to replace these dead cells with new functional cells, thereby providing a cure for devastating neural diseases. The clinical use of neural stem cells (NSCs) for the treatment of neurological diseases requires overcoming the scarcity of the initial in vivo NSC population. Thus, we developed a novel 3-dimentional cellular automata model for optimum production of neural stem cells and their derivatives in large scale to treat neurodegenerative disorder patients.

• Korean Journal of Radiology
• /
• 제24권3호
• /
• pp.247-258
• /
• 2023

Objective: To localize the neuroanatomical substrate of rapid eye movement sleep behavior disorder (RBD) and to investigate the neuroanatomical locational relationship between RBD and α-synucleinopathy neurodegenerative diseases. Materials and Methods: Using a systematic PubMed search, we identified 19 patients with lesions in different brain regions that caused RBD. First, lesion network mapping was applied to confirm whether the lesion locations causing RBD corresponded to a common brain network. Second, the literature-based RBD lesion network map was validated using neuroimaging findings and locations of brain pathologies at post-mortem in patients with idiopathic RBD (iRBD) who were identified by independent systematic literature search using PubMed. Finally, we assessed the locational relationship between the sites of pathological alterations at the preclinical stage in α-synucleinopathy neurodegenerative diseases and the brain network for RBD. Results: The lesion network mapping showed lesions causing RBD to be localized to a common brain network defined by connectivity to the pons (including the locus coeruleus, dorsal raphe nucleus, central superior nucleus, and ventrolateral periaqueductal gray), regardless of the lesion location. The positive regions in the pons were replicated by the neuroimaging findings in an independent group of patients with iRBD and it coincided with the reported pathological alterations at post-mortem in patients with iRBD. Furthermore, all brain pathological sites at preclinical stages (Braak stages 1-2) in Parkinson's disease (PD) and at brainstem Lewy body disease in dementia with Lewy bodies (DLB) were involved in the brain network identified for RBD. Conclusion: The brain network defined by connectivity to positive pons regions might be the regulatory network loop inducing RBD in humans. In addition, our results suggested that the underlying cause of high phenoconversion rate from iRBD to neurodegenerative α-synucleinopathy might be pathological changes in the preclinical stage of α-synucleinopathy located at the regulatory network loop of RBD.

• 한국독성학회:학술대회논문집
• /
• 한국독성학회 2003년도 추계학술대회
• /
• pp.34-63
• /
• 2003

Idiopathic Parkinson's disease (IPD) represents a common neurodegenerative disorder. While epidemiological studies have suggested a number of risk factors including age, gender, race, and inherited disorder, the cumulative evidence supports the view that environmental or occupational exposure to certain chemicals may contribute to the initiation and progress of Parkinsonism.(omitted)

• 한국환경성돌연변이발암원학회지
• /
• 제23권4호
• /
• pp.115-130
• /
• 2003

Idiopathic Parkinson's disease (IPD) represents a common neurodegenerative disorder. While epidemiological studies have suggested a number of risk factors including age, gender, race, and inherited disorder, the cumulative evidence supports the view that environmental or occupational exposure to certain chemicals may contribute to the initiation and progress of Parkinsonism. More recently, clinical and laboratory investigations have led to the theory that dysregulation of iron, an essential metal to body function, may underlie IPD by initiating free radical reaction, diminishing the mitochondrial energy production, and provoking the oxidative cytotoxicity. The participation of iron in neuronal cell death is especially intriguing in that iron acquisition and regulation in brain are highly conservative and thus vulnerable to interference from other metals that bear the similar chemical reactivity. Manganese neurotoxicity, induced possibly by altering iron homeostasis, is such an example. In fact, the current interest in manganese neurotoxicology stems from two primary concerns: its clinical symptoms that resemble Parkinson's disease and its increased use as an antiknock agent to replace lead in gasoline. This article will commence with addressing the current understanding of iron-associated neurodegenerative damage. The major focus will then be devoted to the mechanism whereby manganese alters iron homeostasis in brain.

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

• BMB Reports
• /
• 제50권7호
• /
• pp.345-354
• /
• 2017

Autophagy, a catabolic process necessary for the maintenance of intracellular homeostasis, has recently been the focus of numerous human diseases and conditions, such as aging, cancer, development, immunity, longevity, and neurodegeneration. However, the continued presence of autophagy is essential for cell survival and dysfunctional autophagy is thought to speed up the progression of neurodegeneration. The actual molecular mechanism behind the progression of dysfunctional autophagy is not yet fully understood. Emerging evidence suggests that basal autophagy is necessary for the removal of misfolded, aggregated proteins and damaged cellular organelles through lysosomal mediated degradation. Physiologically, neurodegenerative disorders are related to the accumulation of amyloid ${\beta}$ peptide and ${\alpha}-synuclein$ protein aggregation, as seen in patients with Alzheimer's disease and Parkinson's disease, respectively. Even though autophagy could impact several facets of human biology and disease, it generally functions as a clearance for toxic proteins in the brain, which contributes novel insight into the pathophysiological understanding of neurodegenerative disorders. In particular, several studies demonstrate that natural compounds or small molecule autophagy enhancer stimuli are essential in the clearance of amyloid ${\beta}$ and ${\alpha}-synuclein$ deposits. Therefore, this review briefly deliberates on the recent implications of autophagy in neurodegenerative disorder control, and emphasizes the opportunities and potential therapeutic application of applied autophagy.

• The Korean Journal of Pain
• /
• 제33권1호
• /
• pp.90-96
• /
• 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.

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

• Biomolecules & Therapeutics
• /
• 제29권6호
• /
• pp.605-614
• /
• 2021

Autophagy is an important degradative pathway that eliminates misfolded proteins and damaged organelles from cells. Autophagy is crucial for neuronal homeostasis and function. A lack of or deficiency in autophagy leads to the accumulation of protein aggregates, which are associated with several neurodegenerative diseases. Compared with non-neuronal cells, neurons exhibit rapid autophagic flux because damaged organelles or protein aggregates cannot be diluted in post-mitotic cells; because of this, these cells exhibit characteristic features of autophagy, such as compartment-specific autophagy, which depends on polarized structures and rapid autophagy flux. In addition, neurons exhibit compartment-specific autophagy, which depends on polarized structures. Neuronal autophagy may have additional physiological roles other than amino acid recycling. In this review, we focus on the characteristics and regulatory factors of neuronal autophagy. We also describe intracellular selective autophagy in neurons and its association with neurodegenerative diseases.

• BMB Reports
• /
• 제52권6호
• /
• pp.349-359
• /
• 2019

After the first research declaring the generation of human induced pluripotent stem cells (hiPSCs) in 2007, several attempts have been made to model neurodegenerative disease in vitro during the past decade. Parkinson's disease (PD) is the second most common neurodegenerative disorder, which is mainly characterized by motor dysfunction. The formation of unique and filamentous inclusion bodies called Lewy bodies (LBs) is the hallmark of both PD and dementia with LBs. The key pathology in PD is generally considered to be the alpha-synuclein (${\alpha}$-syn) accumulation, although it is still controversial whether this protein aggregation is a cause or consequence of neurodegeneration. In the present work, the recently published researches which recapitulated the ${\alpha}$-syn aggregation phenomena in sporadic and familial PD hiPSC models were reviewed. Furthermore, the advantages and potentials of using patient-derived PD hiPSC with focus on ${\alpha}$-syn aggregation have been discussed.