11:10-12:00, Rm 103

Autophagy in Pathogenesis of DiseasesBLS1-1Molecular mechanisms of autophagyYong-Keun JungDepartment of Biological Science, Seoul National University, Seoul 151-747, KoreaAutophagy is an intracellular, bulk degradation process in which a portion of cytoplasm issequestered in an autophagosome and subsequently degraded upon fusion with alysosome. Autophagy is an evolutionarily conserved process and is induced by manyforms of stress, including nutrient and energy starvation, oxidative stress, and infections.This process requires the participation of autophagy-related (ATG) proteins. Autophagyplays an essential role in differentiation and development, as well as in cellular responseto stress. Also, autophagy has been associated with neurodegenerative diseases, cancer,pathogen infections, obesity, and myopathies. Although the pro-survival function ofautophagy is best characterized during nutrient deficiency, excessive autophagy mayresult in non-apoptotic cell death, named autophagic cell death that is morphologicallydistinct from apoptosis. Autophagy is also an emerging focus in aging, as it may be aregulatory mechanism via which lifespan is regulated in model organisms. Atg5, firstdiscovered in yeast, is a protein involved in the early stages of autophagosome formationas a form of conjugation with Atg12 and Atg8 (LC3). Further, the role of ATG protein andautophgay activation in catabolic process and human diseases will be discussed.BLS1-4Autophagy and infectious diseasesEun-Kyeong JoInfection Signaling Network Research Center and Department of Microbiology, College ofMedicine, Chungnam National University, Daejeon 301-747, KoreaAutophagy is an intracellular mechanism of protein degradation and a novel antimicrobialstrategy. Recent studies have revealed that autophagy mediates resistance to pathogensand may be a target for immune evasion by viruses and bacteria. Accumulating data onthe connection and molecular mechanisms between innate receptor-mediated innateimmunity and autophagy support a clearer understanding of the exact roles of autophagy.Several immune effectors including cytokines have been suggested to contribute toautophagy activation or inhibition, thereby affecting the outcome of infectious diseases. Ofparticular interest, autophagy activation induced by vitamin D3 contributes toantimycobacterial responses through phagosomal maturation in human macrophages.However, our recent studies using models of mycobacterial infection also provideevidence that excessive autophagy and oxidative stress are detrimental to cell survival. Abetter understanding of the molecular control mechanisms and players of autophagypathways involved in pathogen tactics and the host innate defensive armory is necessaryfor the development of novel vaccines or therapeutic approaches against a variety ofinfectious diseases.BLS1-2Autophagy and ER stress in β-cells and diabetesWenying Quan, Kyu Yeon Hur, Yu-Mi Lim, Jun-Chul Lee, Myung-Shik LeeDepartment of Medicine, Samsung Medical CenterWe have reported that autophagy deficiency in pancreatic β-cells leads to functional andstructural abnormalities of organelles such as the ER. Because ER stress has beenimplicated in the pathogenesis of β-cell failure and diabetes, dysregulated β-cellautophagy may participate in the development of diabetes associated with ER stress. Wereport herein that autophagy-deficient β-cells have compromised ER stress or unfoldedprotein response (UPR) machinery and increased susceptibility to ER stressors. Mice withβ-cell-specific autophagy deficiency that show mild hyperglycemia developed diabeteswhen bred with ob/ob mice to impose ER stress in vivo, which was due to increased β-celldeath and ROS damage. Autophagic activity was enhanced by lipid, while proteolysis wasreduced. These results suggest that autophagy is important for intact UPR machinery andan appropriate UPR, particularly in response to lipid injury. Autophagy deficiency inpancreatic β-cells may contribute to the progression from obesity to diabetes.BLS1-5Autophagy and cancerKyeong Sook ChoiDepartment of Molecular Science & Technology, Institute for Medical Sciences, Ajou UniversitySchool of Medicine, Suwon, KoreaThe role of autophagy in cancer and treatment responsiveness is complicated due to itsdual function as both a tumor suppressor (an anti-tumor mechanism) and a protector ofcancer cell survival (a pro-tumor mechanism). Autophagy activation in particular geneticbackgrounds and/or completion of the autophagic process beyond reversibility of cellviability can lead to cell death, thus enhancing treatment efficacy. On the other hand,pharmacological and/or genetic inhibition of autophagy has been shown to sensitizecancer cells to the lethal effect of different types of stress, suggesting that suppression ofthe autophagic pathway may represent a valuable therapeutic strategy for radio- andchemosensitization. At present, this complex role of autophagy makes it hard to decipherhow to universally modulate autophagy for maximum therapeutic benefit. Thus, for thedevelopment of effective cancer therapeutics via autophagy modulation, elucidation of thespecific role that autophagy plays at different stages of cancer progression, determinationof the cell type or genetic context-dependency, and clarification of the autophagicpathways induced by the therapeutic agents are required.BLS1-3Autophagy and neurodegenerative diseaseHyeung Jin Son, Jung Hee Shim and Kyung Hee KimDepartment of Brain & Cognitive Sciences, Division of Life and Pharmaceutical Sciences, EwhaWomans University, Seoul 120-750, KoreaAutophgy is essential for homeostasis and survival of neurons. The phenotypic analysisof the autophagy-deficient mice demonstrated that Atg5 or Atg7 deficiency in braindevelops neurodegenerative phenotype in selected neuronal populations. Moreoverreduced levels of Beclin 1 have been found in brain tissues of aged, Alzheimer’s andHuntington’s patients. Therefore, insufficient autophagy may also contribute to certainneurodegenerative diseases. Autophagy plays an essential role in an aggregateclearance pathway. Indeed, aggregate-prone proteins, such as alpha-synuclein andsuperoxide dismutase 1 are degraded through autophagy. Recent work has linkeddefects in mitophagy to the familial Parkinson’s disease. Mitophagy is a specificautophagic process to eliminate damaged mitochondria, which is regulated by parkin andPINK1. While autophagy provide a neuroprotective mechanism, there is evidenceshowing that dysfunctional autophagy in certain pathological conditions may trigger andmediated programmed cell death. Therefore, a profound understanding of thephysiological effects and the mechanisms underlying autophagy in neurons under variouspathological conditions might be useful in seeking effective new therapy forneurodegenerative disease.BLS2-1Clinical features and genetic etiology of neurodegenerative diseasesSun Ju ChungParkinson/Alzheimer Center, Department of Neurology, Asan Medical Center, University of UlsanCollege of Medicine, Seoul, KoreaAlzheimer’s disease (AD) and Parkinson’s disease (PD) are common neurodegenerativebrain disorders, having an immense societal impact. In AD, the gradual development offorgetfulness is the major symptom. Once memory disturbance has become pronounced,other cerebral dysfunction become increasingly apparent. Genetically, AD is classifiedinto two forms: 1) familial cases with Mendelian inheritance of predominantly early-onset,and 2) sporadic cases with less apparent of no familial aggregation and usually of lateronset age. Early onset familial AD is caused by mutations in the APP, PSEN1, andPSEN2 genes. Recent genome-wide association study (GWAS) have identified severaladditional AD susceptibility loci that are common in general population. PD is the secondmost common neurodegenerative disorder, characterized by a large number of motor andnon-motor features that can cause functional disability. Over the past 10 years, geneticresearch on PD has changed our conventional wisdom that PD was not a geneticdisorder. Several gene mutations have been identified as causing familial PD. GWAShave become increasingly widely used to determine genomic regions that may containloci influencing the risk of PD, providing new biological insights. The details of recentachievement in the genetics of AD and PD will be presented.88 Korean Society for Biochemistry and Molecular Biology