• Title/Summary/Keyword: brain structure

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Modification and inactivation of Cu,Zn-superoxide dismutase by the lipid peroxidation product, acrolein

  • Kang, Jung Hoon
    • BMB Reports
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    • v.46 no.11
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    • pp.555-560
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    • 2013
  • Acrolein is the most reactive aldehydic product of lipid peroxidation and is found to be elevated in the brain when oxidative stress is high. The effects of acrolein on the structure and function of human Cu,Zn-superoxide dismutase (SOD) were examined. When Cu,Zn-SOD was incubated with acrolein, the covalent crosslinking of the protein was increased, and the loss of enzymatic activity was increased in a dose-dependent manner. Reactive oxygen species (ROS) scavengers and copper chelators inhibited the acrolein-mediated Cu,Zn-SOD modification and the formation of carbonyl compound. The present study shows that ROS may play a critical role in acrolein-induced Cu,Zn-SOD modification and inactivation. When Cu,Zn-SOD that has been exposed to acrolein was subsequently analyzed by amino acid analysis, serine, histidine, arginine, threonine and lysine residues were particularly sensitive. It is suggested that the modification and inactivation of Cu,Zn-SOD by acrolein could be produced by more oxidative cell environments.

Fragile X Mental Retardation Protein in Learning-Related Synaptic Plasticity

  • Mercaldo, Valentina;Descalzi, Giannina;Zhuo, Min
    • Molecules and Cells
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    • v.28 no.6
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    • pp.501-507
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    • 2009
  • Fragile X syndrome (FXS) is caused by a lack of the fragile X mental retardation protein (FMRP) due to silencing of the Fmr1 gene. As an RNA binding protein, FMRP is thought to contribute to synaptic plasticity by regulating plasticity-related protein synthesis and other signaling pathways. Previous studies have mostly focused on the roles of FMRP within the hippocampus - a key structure for spatial memory. However, recent studies indicate that FMRP may have a more general contribution to brain functions, including synaptic plasticity and modulation within the prefrontal cortex. In this brief review, we will focus on recent studies reported in the prefrontal cortex, including the anterior cingulate cortex (ACC). We hypothesize that alterations in ACC-related plasticity and synaptic modulation may contribute to various forms of cognitive deficits associated with FXS.

Novel Lead Optimization Strategy Using Quantitative Structure-Activity Relationship and Physiologically-Based Pharmacokinetics Modeling (정량적 구조-활성 상관 관계와 생리학 기반 약물동태를 사용한 새로운 선도물질 최적화 전략)

  • Byeon, Jin-Ju;Park, Min-Ho;Shin, Seok-Ho;Shin, Young Geun
    • YAKHAK HOEJI
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    • v.59 no.4
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    • pp.151-157
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    • 2015
  • The purpose of this study is to demonstrate how lead compounds are best optimized with the application of in silico QSAR and PBPK modeling at the early drug discovery stage. Several predictive QSAR models such as $IC_{50}$ potency model, intrinsic clearance model and brain penetration model were built and applied to a set of virtually synthesized library of the BACE1 inhibitors. Selected candidate compounds were also applied to the PBPK modeling for comparison between the predicted animal pharmacokinetic parameters and the observed ones in vivo. This novel lead optimization strategy using QSAR and PBPK modelings could be helpful to expedite the drug discovery process.

Current Understanding in Neurobiology of Depressive Disorders : Imaging Genetic Studies on Serotonin Transporter (우울장애의 신경생물학적 최신 지견 : 세로토닌 전달체에 대한 영상 유전학적 연구를 중심으로)

  • Ham, Byung-Joo
    • Korean Journal of Biological Psychiatry
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    • v.18 no.4
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    • pp.176-180
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    • 2011
  • Depressive disorders have strong genetic components. However, conventional linkage and association studies have not yielded definitive results. These might be due to the absence of objective diagnostic tests, the complex nature of human behavior or the incomplete penetrance of psychiatric traits. Imaging genetics explores the influences of genetic variation on the brain function or structure. This technique could provide a more sensitive assessment than traditional behavioral measures in psychiatric studies. Imaging genetics is a relatively new field of psychiatric researches, and may improve our understanding on neurobiology of psychiatric disorders. In this review, current understanding in neurobiology of depressive disorders, especially imaging genetic studies on serotonin transporter will be discussed.

Precise assembly and regulation of 26S proteasome and correlation between proteasome dysfunction and neurodegenerative diseases

  • Im, Eunju;Chung, Kwang Chul
    • BMB Reports
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    • v.49 no.9
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    • pp.459-473
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    • 2016
  • Neurodegenerative diseases (NDs) often involve the formation of abnormal and toxic protein aggregates, which are thought to be the primary factor in ND occurrence and progression. Aged neurons exhibit marked increases in aggregated protein levels, which can lead to increased cell death in specific brain regions. As no specific drugs/therapies for treating the symptoms or/and progression of NDs are available, obtaining a complete understanding of the mechanism underlying the formation of protein aggregates is needed for designing a novel and efficient removal strategy. Intracellular proteolysis generally involves either the lysosomal or ubiquitin-proteasome system. In this review, we focus on the structure and assembly of the proteasome, proteasome-mediated protein degradation, and the multiple dynamic regulatory mechanisms governing proteasome activity. We also discuss the plausibility of the correlation between changes in proteasome activity and the occurrence of NDs.

Monoamine Oxidase Inhibitors from Basidiomycete 8082

  • Lee, In-Kyoung;Yun, Bong-Sik;Kim, Yung-Ho;Lee, Myung-Koo;Yoo, Ick-Dong
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1998.11a
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    • pp.132-132
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    • 1998
  • It has been known that MAO (monoamine oxidase) catalyses the oxidation of endogenous neurotransmitter amines. From its key role in the regulation of some physiological amines, it has been the target of inhibitors used as antidepressive agents. In our continuing search for MAO inhibitors from Basidiomycete. sp., strain 8082 was selected. Two metabolites (8082-1 and 8082-2) were isolated by adsorption chromatography and HPLC from the culture broth of strain 8082. The structure of 8082-1 and 8082-2 were elucidated by $^1$H-, $\^$13/C-NMR and HMBC spectral data, and these products were identified as 5-methylmellein and nectriapyrone, respectively, which have significant inhibitory effect against mouse brain MAO.

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Acrolein, A Reactive Product of Lipid Peroxidation, Induces Oxidative Modification of Cytochrome c

  • Kang, Jung Hoon
    • Bulletin of the Korean Chemical Society
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    • v.34 no.11
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    • pp.3295-3300
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    • 2013
  • Acrolein (ACR) is a well-known carbonyl toxin produced by lipid peroxidation of polyunsaturated fatty acids, which is involved in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). In Alzheimer's brain, ACR was found to be elevated in hippocampus and temporal cortex where oxidative stress is high. In this study, we evaluated oxidative modification of cytochrome c occurring after incubation with ACR. When cytochrome c was incubated with ACR, protein aggregation increased in a dose-dependent manner. The formation of carbonyl compounds and the release of iron were obtained in ACR-treated cytochrome c. Reactive oxygen species scavengers and iron specific chelator inhibited the ACR-mediated cytochrome c modification and carbonyl compound formation. Our data demonstrate that oxidative damage of cytochrome c by ACR might induce disruption of cyotochrome c structure and iron mishandling as a contributing factor to the pathology of AD.

In vitro Screening of Oxime Reactivators on the Model of Paraoxon-inhibited Acetylcholinesterase-SAR Study

  • Holas, Ondrej;Musilek, Kamil;Pohanka, Miroslav;Kuca, Kamil;Opletalova, Veronika;Jung, Young-Sik
    • Bulletin of the Korean Chemical Society
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    • v.31 no.6
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    • pp.1609-1614
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    • 2010
  • Acetylcholinesterase reactivators are crucial antidotes for the treatment of organophosphate intoxication. Standard in vitro test was chosen using a rat brain homogenate as the source of AChE. Screening of reactivation potency was performed with two concentration of reactivator (1000 ${\mu}M$ and 10 ${\mu}M$). Results were compared to established reactivators pralidoxime, methoxime, HI-6, trimedoxime and obidoxime. More than 30 novel reactivators performed equal or better reactivation ability of POX-inhibited AChE compared to currently used reactivators. The structure-activity relationship for reactivators of paraoxon-inhibited AChE was developed.

A Study on Embodiment of Evolving Cellular Automata Neural Systems using Evolvable Hardware

  • Sim, Kwee-Bo;Ban, Chang-Bong
    • Journal of the Korean Institute of Intelligent Systems
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    • v.11 no.8
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    • pp.746-753
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    • 2001
  • In this paper, we review the basic concept of Evolvable Hardware first. And we examine genetic algorithm processor and hardware reconfiguration method and implementation. By considering complexity and performance of hardware at the same time, we design genetic algorithm processor using modularization and parallel processing method. And we design frame that has connection structure and logic block on FPGA, and embody reconfigurable hardware that do so that this frame may be reconstructed by RAM. Also we implemented ECANS that information processing system such as living creatures'brain using this hardware reconfiguration method. And we apply ECANS which is implemented using the concept of Evolvable Hardware to time-series prediction problem in order to verify the effectiveness.

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