• BMB Reports
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• v.53 no.1
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• pp.47-55
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• 2020

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease and has become a major socioeconomic issue in many developed countries. Currently available therapeutic agents for AD provide only symptomatic treatments, mainly because the complete mechanism of the AD pathogenesis is still unclear. Although several different hypotheses have been proposed, mitochondrial dysfunction has gathered interest because of its profound effect on brain bioenergetics and neuronal survival in the pathophysiology of AD. Various therapeutic agents targeting the mitochondrial pathways associated with AD have been developed over the past decade. Although most of these agents are still early in the clinical development process, they are used to restore mitochondrial function, which provides an alternative therapeutic strategy that is likely to slow the progression of the disease. In this mini review, we will survey the AD-related mitochondrial pathways and their small-molecule modulators that have therapeutic potential. We will focus on recently reported examples, and also overview the current challenges and future perspectives of ongoing research.

• Molecules and Cells
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• v.41 no.8
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• pp.724-732
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• 2018

Plant defence responses to various biotic stresses via systemic acquired resistance (SAR) are induced by avirulent pathogens and chemical compounds, including certain plant hormones in volatile form, such as methyl salicylate and methyl jasmonate. SAR refers to the observation that, when a local part of a plant is exposed to elicitors, the entire plant exhibits a resistance response. In the natural environment, plants are continuously exposed to avirulent pathogens that induce SAR and volatile emissions affecting neighbouring plants as well as the plant itself. However, the underlying mechanism has not been intensively studied. In this study, we evaluated whether plants "memorise" the previous activation of plant immunity when exposed repeatedly to plant defensive volatiles such as methyl salicylate and methyl jasmonate. We hypothesised that stronger SAR responses would occur in plants treated with repeated applications of the volatile plant defence compound MeSA than in those exposed to a single or no treatment. Nicotiana benthamiana seedlings subjected to repeated applications of MeSA exhibited greater protection against Pseudomonas syringae pv. tabaci and Pectobacterium carotovorum subsp. carotovorum than the control. The increase in SAR capacity in response to repeated MeSA treatment was confirmed by analysing the defence priming of the expression of N. benthamiana Pathogenesis-Related 1a (NbPR1a) and NbPR2 by quantitative reverse-transcription PCR compared with the control. We propose the concept of plant memory of plant defence volatiles and suggest that SAR is strengthened by the repeated perception of volatile compounds in plants.

• The Plant Pathology Journal
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• v.21 no.4
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• pp.395-401
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• 2005

The dlm (disease lesion mimic) mutant of soybean (Glycine max L. Merr) shows the similar lesion of a soybean disease caused by a fungus, Corynespora cassilcola. The lesion was examined at cellular and molecular level. Trypan blue staining result indicated that cell death was detectable in the entire region of leaves excluding veins when the lesions had already been developed. We found that the mesophyll cells of palisade layer in the dim mutant appeared to be wider apart from each other. The chloroplasts of the dim mutant cells contained bigger starch granules than those in normal plants. We also found that the lesion development of dlm plant was light-dependent and the starch degradation during the dark period of diurnal cycle was impaired in the mutant. Three soybean pathogenesis-related genes, PR-1a, PR-4, and PR-10, were examined for their expression patterns during the development of disease lesion mimic. The expression of all three genes was up-regulated to some extent upon the appearance of the disease lesion mimic. Although the exact function of DLM protein remains elusive, our data would provide some insight into mechanism underling the cell death associated with the dim mutation.

• Biomolecules & Therapeutics
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• v.20 no.3
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• pp.245-255
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• 2012

Amyloid-${\beta}$ peptide ($A{\beta}$) is still best known as a molecule to cause Alzheimer's disease (AD) through accumulation and deposition within the frontal cortex and hippocampus in the brain. Thus, strategies on developing AD drugs have been focused on the reduction of $A{\beta}$ in the brain. Since accumulation of $A{\beta}$ depends on the rate of its synthesis and clearance, the metabolic pathway of $A{\beta}$ in the brain and the whole body should be carefully explored for AD research. Although the synthetic pathway of $A{\beta}$ is equally important, we summarize primarily the clearance pathway in this paper because the former has been extensively reviewed in previous studies. The clearance of $A{\beta}$ from the brain is accomplished by several mechanisms which include non-enzymatic and enzymatic pathways. Nonenzymatic pathway includes interstitial fluid drainage, uptake by microglial phagocytosis, and transport across the blood vessel walls into the circulation. Multiple $A{\beta}$-degrading enzymes (ADE) implicated in the clearance process have been identified, which include neprilysin, insulin-degrading enzyme, matrix metalloproteinase-9, glutamate carboxypeptidase II and others. A series of studies on $A{\beta}$ clearance mechanism provide new insight into the pathogenesis of AD at the molecular level and suggest a new target for the development of novel therapeutics.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.10 no.3
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• pp.648-653
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• 2009

p62 is a key component of protein aggregates found in brains of neurodegenerative diseases in which oxidative stress is involved in the pathogenesis. p62 was induced in SH-SY5Y, a neuroblastoma cell line, by hydroxydoparnine or $C_2-ceramide$ known to be related to neurodegenerative diseases. The over-expression of p62 showed the neuroprotective effect against the ceramide induced cell death. In addition, p62 became insoluble and cleaved forms as time proceeded after the ceramide treatment, suggesting the mechanism by which p62 is associated with aggregates in neurodegenerative diseases.

• Journal of Oral Medicine and Pain
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• v.25 no.2
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• pp.223-228
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• 2000

The relationship between TMD and otologic symptoms such as tinnitus, vertigo and dizziness has been noted for many years. The existence of otologic symptoms in patients with TMD can be explained by the anatomic proximity and embryologic origin of the structures of the ear and the temporomandibular joint, however the pathogenesis of the symptoms is poorly understood. Serveral hypotheses have been proposed. : Eustachian tube hypothesis, the tensor tympani hypothesis, the otomandibular ligament hypothesis, excessive somatic concern hypothesis. Some investigators have reported that palpation of the deep masseter muscle, sternocleidomastoid muscle or clenching can intensify a patient's tinnitus and in that case, TMD therapy would improve their otologic symptoms. Although tinnitus and vertigo are common symptoms in the general population and also increase with increasing age, those are highly significantly associated with TMD compared with control group. This case report describes the possible mechanism and management of otologic symptoms in patient with TMD who has visited our clinic complaining asymmetric tinnitus and dull pain on her left masseter muscle.

• BMB Reports
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• v.54 no.10
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• pp.522-527
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• 2021

Lysine-specific demethylase 1 (LSD1) is an epigenetic regulator that modulates the chromatin status, contributing to gene activation or repression. The post-translational modification of LSD1 is critical for the regulation of many of its biological processes. Phosphorylation of serine 112 of LSD1 by protein kinase C alpha (PKCα) is crucial for regulating inflammation, but its physiological significance is not fully understood. This study aimed to investigate the role of Lsd1-S112A, a phosphorylation defective mutant, in the cigarette smoke extract/LPS-induced chronic obstructive pulmonary disease (COPD) model using Lsd1^SA/SA mice and to explore the potential mechanism underpinning the development of COPD. We found that Lsd1^SA/SA mice exhibited increased susceptibility to CSE/LPS-induced COPD, including high inflammatory cell influx into the bronchoalveolar lavage fluid and airspace enlargement. Additionally, the high gene expression associated with the inflammatory response and oxidative stress was observed in cells and mice containing Lsd1-S112A. Similar results were obtained from the mouse embryonic fibroblasts exposed to a PKCα inhibitor, Go6976. Thus, the lack of LSD1 phosphorylation exacerbates CSE/LPS-induced COPD by elevating inflammation and oxidative stress.

• BMB Reports
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• v.54 no.9
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• pp.439-450
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• 2021

Translating ribosomes accompany co-translational regulation of nascent polypeptide chains, including subcellular targeting, protein folding, and covalent modifications. Ribosome-associated quality control (RQC) is a co-translational surveillance mechanism triggered by ribosomal collisions, an indication of atypical translation. The ribosome-associated E3 ligase ZNF598 ubiquitinates small subunit proteins at the stalled ribosomes. A series of RQC factors are then recruited to dissociate and triage aberrant translation intermediates. Regulatory ribosomal stalling may occur on endogenous transcripts for quality gene expression, whereas ribosomal collisions are more globally induced by ribotoxic stressors such as translation inhibitors, ribotoxins, and UV radiation. The latter are sensed by ribosome-associated kinases GCN2 and ZAKα, activating integrated stress response (ISR) and ribotoxic stress response (RSR), respectively. Hierarchical crosstalks among RQC, ISR, and RSR pathways are readily detectable since the collided ribosome is their common substrate for activation. Given the strong implications of RQC factors in neuronal physiology and neurological disorders, the interplay between RQC and ribosome-associated stress signaling may sustain proteostasis, adaptively determine cell fate, and contribute to neural pathogenesis. The elucidation of underlying molecular principles in relevant human diseases should thus provide unexplored therapeutic opportunities.

• Journal of Microbiology and Biotechnology
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• v.31 no.2
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• pp.226-232
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• 2021

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging phlebovirus of the Phenuiviridae family that has been circulating in the following Asian countries: Vietnam, Myanmar, Taiwan, China, Japan, and South Korea. Despite the increasing infection rates and relatively high mortality rate, there is limited information available regarding SFTSV pathogenesis. In addition, there are currently no vaccines or effective antiviral treatments available. Previous reports have shown that SFTSV suppresses the host immune response and its nonstructural proteins (NSs) function as an antagonist of type I interferon (IFN), whose induction is an essential part of the host defense system against viral infections. Given that SFTSV NSs suppress the innate immune response by inhibiting type I IFN, we investigated the mechanism utilized by SFTSV NSs to evade IFNmediated response. Our co-immunoprecipitation data suggest the interactions between NSs and retinoic acid inducible gene-I (RIG-I) or TANK binding kinase 1 (TBK1). Furthermore, confocal analysis indicates the ability of NSs to sequester RIG-I and related downstream molecules in the cytoplasmic structures called inclusion bodies (IBs). NSs are also capable of inhibiting TBK1-interferon regulatory factor 3 (IRF3) interaction, and therefore prevent the phosphorylation and nuclear translocation of IRF3 for the induction of type I IFN. The ability of SFTSV NSs to interact with and sequester TBK1 and IRF3 in IBs demonstrate an effective yet unique method utilized by SFTSV to evade and suppress host immunity.

• Microbiology and Biotechnology Letters
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• v.50 no.1
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• pp.1-14
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• 2022

Bacteria communicate with each other through an intricate communication mechanism known as quorum sensing (QS). QS regulates different behavioral aspects in bacteria, such as biofilm formation, sporulation, virulence gene expression, antibiotic production, and bioluminescence. Several different chemical signals and signal detection systems play vital roles in promoting highly efficient intra- and interspecies communication. Gram-negative bacteria coordinate gene regulation through the production of acyl homoserine lactones (AHLs). Gram-positive bacteria do not code for AHL production, while some gram-negative bacteria have an incomplete AHL-QS system. Despite this fact, these microbes can detect AHLs owing to the presence of LuxR solo receptors. Various studies have reported the role of AHLs in interspecies signaling. Moreover, as bacteria live in a polymicrobial community, the production of extracellular compounds to compete for resources is imperative. Thus, AHL-mediated signaling and inhibition are considered to affect virulence in bacteria. In the current review, we focus on the synthesis and regulation mechanisms of AHLs and highlight their role in interspecies bacterial signaling. Exploring interspecies bacterial signaling will further help us understand host-pathogen interactions, thereby contributing to the development of therapeutic strategies intended to target chronic polymicrobial infections.