• Journal of Integrative Natural Science
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• v.6 no.3
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• pp.125-137
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• 2013

Promising evidence suggests that amyloid beta peptide ($A{\beta}$), a key mediator in age-dependent neuronal and cerebrovascular degeneration, activates death signalling processes leading to neuronal as well as non-neuronal cell death in the central nervous system. A major cellular event in $A{\beta}$-induced apoptosis of non-neuronal cells, including cerebral endothelial cells, astrocytes and oligodendrocytes, is mitochondrial dysfunction. The apoptosis signalling cascade upstream of mitochondria entails $A{\beta}$ activation of neutral sphingomyelinase, resulting in the release of ceramide from membrane sphingomyelin. Ceramide then activates protein phosphatase 2A (PP2A), a member in the ceramide-activated protein phosphatase (CAPP) family. PP2A dephosphorylation of Akt and FKHRL1 plays a pivotal role in $A{\beta}$-induced Bad translocation to mitochondria and transactivation of Bim. Bad and Bim are pro-apoptotic proteins that cause mitochondrial dysfunction characterized by excessive ROS formation, mitochondrial DNA (mtDNA) damage, and release of mitochondrial apoptotic proteins including cytochrome c, apoptosis inducing factor (AIF), endonuclease G and Smac. The cellular events activated by $A{\beta}$ to induce death of non-neuronal cells are complex. Understanding these apoptosis signalling processes will aid in the development of more effective strategies to slow down age-dependent cerebrovascular degeneration caused by progressive cerebrovascular $A{\beta}$ deposition.

• 대한약리학회:학술대회논문집
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• 2006.10a
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• pp.107.2-107.2
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• 2006

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.65-66
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• 2003

The cause of Huntington's disease (HD) is a pathological expansion of the polyglutamine domain within the N-terminal region of huntingtin. Neuronal aggregates composed of mutant huntingtin within certain neuronal populations are a characteristic hallmark of HD. Because tissue transglutaminase (tTG) cross-links proteins into aggregates and polypeptide-bound glutamines are primary determining factors for tTG-catalyzed reactions, it has been hypothesized that tTG may contribute to the formation of aggregates. (omitted)

• 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)

• Molecules and Cells
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• v.45 no.11
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• pp.781-788
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• 2022

Proline plays a multifaceted role in protein synthesis, redox balance, cell fate regulation, brain development, and other cellular and physiological processes. Here, we focus our review on proline metabolism in neurons, highlighting the role of dysregulated proline metabolism in neuronal dysfunction and consequently neurological and psychiatric disorders. We will discuss the association between genetic and protein function of enzymes in the proline pathway and the development of neurological and psychiatric disorders. We will conclude with a potential mechanism of proline metabolism in neuronal function and mental health.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.4
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• pp.299-306
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• 2013

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been widely used as a treatment for the movement disturbances caused by Parkinson's disease (PD). Despite successful application of DBS, its mechanism of therapeutic effect is not clearly understood. Because PD results from the degeneration of dopamine neurons that affect the basal ganglia (BG) network, investigation of neuronal responses of BG neurons during STN DBS can provide informative insights for the understanding of the mechanism of therapeutic effect. However, it is difficult to observe neuronal activity during DBS because of large stimulation artifacts. Here, we report the observation of neuronal activities of the globus pallidus (GP) in normal and PD model rats during electrical stimulation of the STN. A custom artifact removal technique was devised to enable monitoring of neural activity during stimulation. We investigated how GP neurons responded to STN stimulation at various stimulation frequencies (10, 50, 90 and 130 Hz). It was observed that activities of GP neurons were modulated by stimulation frequency of the STN and significantly inhibited by high frequency stimulation above 50 Hz. These findings suggest that GP neuronal activity is effectively modulated by STN stimulation and strongly dependent on the frequency of stimulation.

• Korean Journal of Pharmacognosy
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• v.42 no.2
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• pp.175-181
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• 2011

Oxidative stress or accumulation of reactive oxygen species (ROS) leads neuronal cellular death and dysfunction, and it contributes to neuronal degenerative disease such as Alzheimer's disease, Parkinson's disease and stroke. Glutamate is one of the major excitatory neurotransmitter in the central nervous system (CNS). Glutamate contributes to fast synaptic transmission, neuronal plasticity, outgrowth and survival, behavior, learning and memory. In spite of these physiological functions, high concentration of glutamate causes neuronal cell damage, acute insults and chronic neuronal neurodegenerative diseases. Heme oxygenase-1 (HO-1) enzyme plays an important role of cellular antioxidant system against oxidant injury. NNMBS020, the water-insoluble fraction of the 70% EtOH extract of root barks of Dictamnus dasycarpus, showed dominant neuroprotective effects on glutamate-induced neurotoxicity in mouse hippocampal HT22 cells by induced the expression of HO-1 and increased HO activity. In mouse hippocampal HT22 cells, NNMBS020 makes the nuclear accumulation of Nrf2 and stimulates extracellular signal-regulated kinase (ERK) pathway. The ERK MAPK pathway inhibitor significantly reduced NNMBS020-induced HO-1 expression, whereas the JNK and p38 inhibitors did not. In conclusion, the water-insoluble fraction of the 70% EtOH extract of root barks of D. dasycarpus (NNMBS020) significantly protect glutamate-induced oxidative damage by induction of HO-1 via Nrf2 and ERK pathway in mouse hippocampal HT22 cells.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.94.3-95
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• 2003

Familial form of Alzheimer's disease (FAD) is caused by mutations in presenilin-l (PS-1) and presenilin-2 (PS-2). PS1 and PS2 mutation are known to similar effects on the production of amyloid peptide (A ) and cause of neuronal cell dath in the brain of patient of Alzheimer's disease. The importance of the alternation of cellular calcium homeostasis in the neuronal cell death by PS1 mutation in a variety of experimental systems has been demonstrated. However, no studies on the effect of PS2 of mutant PS2 on cellular calcium homeostasis, and relevance of its change to neuronal cell vulnerability against neurotoxins have been reported. (omitted)

• Journal of Applied Biological Chemistry
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• v.65 no.1
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• pp.23-31
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• 2022

Oxidative stress and neuroinflammation play important roles in the pathogenesis of Alzheimer's disease (AD). This study investigated the protective effects of paeoniflorin (PF) against neuronal oxidative stress and neuroinflammation in lipopolysaccharide (LPS)-induced mice. The brains of LPS-injected control group showed significantly increased neuroinflammation by activating the nuclear factor kappa B (NF-κB) pathway and increasing inflammatory mediators. However, administration of PF significantly attenuated oxidative stress by inhibiting lipid peroxidation, nitric oxide levels, and reactive oxygen species production in the brain; PF at doses of 5 and 10 mg/kg/day downregulated the expression of NF-κB pathway-related proteins and significantly decreased inflammatory mediators including inducible nitric oxide synthase and cyclooxygenase-2. Moreover, the levels of brain-derived neurotrophic factor and its receptor, tropomycin receptor kinase B, were significantly increased in PF-treated mice. Furthermore, acetylcholinesterase activity and the ration of B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X were significantly reduced by PF in the brains of LPS-induced mice, resulting in the inhibition of cholinergic dysfunction and neuronal apoptosis. Thus, we can conclude that administration of PF to mice prevents the development of LPS-induced AD pathology through the inhibition of neuronal oxidative stress and neuroinflammation, suggesting that PF has a therapeutic potential for AD.

• Korean Journal of Microbiology
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• v.42 no.1
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• pp.73-76
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• 2006

Neuronal precursor cells may provide for cell replacement or gene delivery vehicles in neurodegenerative disease therapy. One impediment to treating neuronal diseases is finding ways to introduce genes into neurons effectively. It is shown here that fiber-modified adenovirus vector delivered gene to neuronal precursor as well as differentiated neuronal cells more efficiently than first-generation adenoviral vector. Moreover, fiber-modified adenoviral vector transduced precursor cells retained the potential for differentiation into neurons and glia in vitro. These results show the potential of modified adenoviral vector in the improved gene delivery to neurons in direct gene therapy protocols. In addition it holds promise for the use of genetically manipulated stem cells for the therapy of neuronal diseases.