• Biomedical Science Letters
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• v.27 no.3
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• pp.182-186
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• 2021

Parkinson disease (PD) is becoming one of the most neurodegenerative disorder worldwide. The deposited aggregates have been connected in the pathophysiology of PD, which are degraded either by ubiquitin-proteasomal system (UPS) or autophagy-lysosomal pathway (ALP). Leucin-rich repeat kinase 2 (LRRK2), one of the neurodegenerative proteins of PD is also stringently controlled by both UPS and ALP degradation as well. However, the polyubiquitination pattern of LRRK2 aggregates is largely unknown. Here, we found that K63-linked polyubiquitinations of G2019S mutant, most familial variant for PD, is highly enhanced compared to those of wild type LRRK2 (WT). In addition, in the presence of overexpressed p62/SQSTM-1, ubiquitination of LRRK2 WT or D1994A was reduced, whereas G2019S mutant was not diminished significantly. Therefore, we propose that degradation of G2019S via UPS is more involved with K63-linked ubiquitination than K48-linked ubiquitination, and overexpressed p62/SQSTM-1 does not enhance degradative effect on G2019S variant.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.196.2-197
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• 2003

Parkinson's disease (PO) is a widespread neurodegenerative disorder. Even though PD has been studied in many aspects, it is still unknown the molecular signaling mechanisms linking reactive oxygen species (ROS) and neuronal apoptosis in PD. A better understanding of cellular mechanisms that occur in Parkinson's disease is essential for development of new therapies. In this study we investigated the signaling molecules involved in neuronal apoptosis induced by 6-hydroxydopamine (6-OHDA) in human SK-N-SH neuroblastoma cells as a model cellular system. (omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.151.1-151.1
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• 2003

Polyunsaturated fatty acids (PUFAs) play many important physiological roles on cellular process through the regulations of intracellular signaling. Recent clinical studies suggest that PUFAs such as n-3 fatty acids (docosahexaenoic acid, 22:6 and a-lnolenic acid, 18:3) may reduce the risk of incident Alzheimer's disease (AD). And also the reports regarding the decrease of n-3 fatty acids in AD brain support the correlation between PUFAs and AD. AD is a neurodegenerative disorder with pathological hallmarks of amyloid plaques and neurofibrillary tangles. (omitted)

• Annals of Clinical Neurophysiology
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• v.6 no.1
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• pp.1-13
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• 2004

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that primarily affects motor neurons. The characteristic features of this devastating disorder are the simultaneous presence of upper and lower motor neuron (LMN) signs with progression from one region of the neuraxis to the next and eventual death, typically from respiratory compromise. Electrophysiological studies are an indispensible part of the ALS evaluation, especially serving as an extension of the clinical examination, and most useful in identifying LMN dysfunction. Not only may electrodiagnostic studies reveal characteristic changes in those regions clinically manifesting signs, but it also serves to disclose asymptomatic areas of involvement.

• Korean Journal of Biological Psychiatry
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• v.3 no.1
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• pp.3-13
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• 1996

Many studies have been conducted to search for the anatomical abnormalities in the brain which ore etiologically related with schizophrenia. Generally schizophrenia in known to be related with decreased brain tissue, hypofrontality and abnormalities in the temporal lobe including the hippocamypus, the agmygdala and the entorhinal cortex. Other areas related with the disorder ore basal ganglia, thalamus, brain stem, pons and nucleus accumbens. Abnormality in brain asymmetry is one of the new areas of interest which needs further study. The results so for ore inconsistent and it is unlikely that the abnormality in one structure is the only cause of the disorder. Rather, schizophrenia develops from the impairment of the parallel processing of integrated and reciprocal information which is distributed to the multiple structures. Histopathologic studies in the postmortem brain suggest that schizophrenia is related with neurodevelopmental abnormality rather than neurodegenerative abnormality.

• Journal of Korean Medical Science
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• v.33 no.47
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• pp.300.1-300.17
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• 2018

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Although its major manifestation is motor symptoms, resulting from the loss of dopaminergic neurons in the substantia nigra, psychiatric symptoms, such as depression, anxiety, hallucination, delusion, apathy and anhedonia, impulsive and compulsive behaviors, and cognitive dysfunction, may also manifest in most patients with PD. Given that the quality of life - and the need for institutionalization - is so highly dependent on the psychiatric well-being of patients with PD, psychiatric symptoms are of high clinical significance. We reviewed the prevalence, risk factors, pathophysiology, and treatment of psychiatric symptoms to get a better understanding of PD for improved management.

• Molecules and Cells
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• v.40 no.7
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• pp.450-456
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• 2017

Mammalian physiology and behavior are regulated by an internal time-keeping system, referred to as circadian rhythm. The circadian timing system has a hierarchical organization composed of the master clock in the suprachiasmatic nucleus (SCN) and local clocks in extra-SCN brain regions and peripheral organs. The circadian clock molecular mechanism involves a network of transcription-translation feedback loops. In addition to the clinical association between circadian rhythm disruption and mood disorders, recent studies have suggested a molecular link between mood regulation and circadian rhythm. Specifically, genetic deletion of the circadian nuclear receptor Rev-$erb{\alpha}$ induces mania-like behavior caused by increased midbrain dopaminergic (DAergic) tone at dusk. The association between circadian rhythm and emotion-related behaviors can be applied to pathological conditions, including neurodegenerative diseases. In Parkinson's disease (PD), DAergic neurons in the substantia nigra pars compacta progressively degenerate leading to motor dysfunction. Patients with PD also exhibit non-motor symptoms, including sleep disorder and neuropsychiatric disorders. Thus, it is important to understand the mechanisms that link the molecular circadian clock and brain machinery in the regulation of emotional behaviors and related midbrain DAergic neuronal circuits in healthy and pathological states. This review summarizes the current literature regarding the association between circadian rhythm and mood regulation from a chronobiological perspective, and may provide insight into therapeutic approaches to target psychiatric symptoms in neurodegenerative diseases involving circadian rhythm dysfunction.

• Molecules and Cells
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• v.38 no.9
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• pp.806-813
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• 2015

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the glucocerebrosidase gene (GBA), which encodes the lysosomal enzyme glucosylceramidase (GCase). Deficiency in GCase leads to characteristic visceral pathology and lethal neurological manifestations in some patients. Investigations into neurogenesis have suggested that neurodegenerative disorders, such as GD, could be overcome or at least ameliorated by the generation of new neurons. Bone marrowderived mesenchymal stem cells (BM-MSCs) are potential candidates for use in the treatment of neurodegenerative disorders because of their ability to promote neurogenesis. Our objective was to examine the mechanism of neurogenesis by BM-MSCs in GD. We found that neural stem cells (NSCs) derived from a neuronopathic GD model exhibited decreased ability for self-renewal and neuronal differentiation. Co-culture of GBA-deficient NSCs with BM-MSCs resulted in an enhanced capacity for self-renewal, and an increased ability for differentiation into neurons or oligodendrocytes. Enhanced proliferation and neuronal differentiation of GBA-deficient NSCs was associated with elevated release of macrophage colony-stimulating factor (M-CSF) from BM-MSCs. Our findings suggest that soluble M-CSF derived from BM-MSCs can modulate GBA-deficient NSCs, resulting in their improved proliferation and neuronal differentiation.

• IMMUNE NETWORK
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• v.11 no.5
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• pp.227-244
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• 2011

MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively regulate gene expression via degradation or translational repression of their target messenger RNAs (mRNAs). Recent studies have clearly demonstrated that miRNAs play critical roles in several biologic processes, including cell cycle, differentiation, cell development, cell growth, and apoptosis and that miRNAs are highly expressed in regulatory T (Treg) cells and a wide range of miRNAs are involved in the regulation of immunity and in the prevention of autoimmunity. It has been increasingly reported that miRNAs are associated with various human diseases like autoimmune disease, skin disease, neurological disease and psychiatric disease. Recently, the identification of miRNAs in skin has added a new dimension in the regulatory network and attracted significant interest in this novel layer of gene regulation. Although miRNA research in the field of dermatology is still relatively new, miRNAs have been the subject of much dermatological interest in skin morphogenesis and in regulating angiogenesis. In addition, miRNAs are moving rapidly center stage as key regulators of neuronal development and function in addition to important contributions to neurodegenerative disorder. Moreover, there is now compelling evidence that dysregulation of miRNA networks is implicated in the development and onset of human neruodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, Down syndrome, depression and schizophrenia. In this review, I briefly summarize the current studies about the roles of miRNAs in various autoimmune diseases, skin diseases, psychoneurological disorders and mental stress.

• Molecular & Cellular Toxicology
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• v.1 no.1
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• pp.40-45
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• 2005

Ursodeoxycholic acid (UDCA) has long been used as an adjuvant or first choice of therapy for liver disease. Commonly, UDCA has been reported to play a role in improving hyperbilirubinemia and disorder of bromsulphalein. More commonly, UDCA has been used in reducing the rate of cholesterol level in bile juice that can cause cholesterol stone. The effects on the promotion of bile acid release that leads an excretion of toxic materials and wastes produced in liver cells as well as various arrays of liver disease such as hepatitis. Other than already reported in clinical use, immunosuppressive effect has been studied, especially in transplantation. In the study, we hypothesized that UDCA might have a certain role in anti-inflammation through a preventive effect of pro-inflammatory potentials in the brain macrophages, microglia. We found that the treatment of $200\;{\mu}g/ml$ UDCA effectively suppressed the pro-inflammatory mediators (i.e. nitric oxide and interleukin-$1{\beta}$) in rat microglia compared to comparators. Interestingly, RT-PCR analysis suggested that UDCA strongly attenuated the expression of $IL-1{\beta}$ that was comparable with cyclosporine A at 48 h incubation. Conclusively, we found that UDCA may playa cytoprotective role in microglial cells through direct or indirect pathways by scavenging a toxic compound or an anti-inflammatory effect, which are known as major causes of neurodegenerative diseases.