https://scholar.dgist.ac.kr/handle/20.500.11750/314 2026-04-09T11:47:55Z 2026-04-09T11:47:55Z Lee, Sung Bae https://scholar.dgist.ac.kr/handle/20.500.11750/14828 2025-07-25T03:32:12Z 2018-08-08T15:00:00Z

Title: Molecular and Cellular mechanisms of protein toxicity in neurodegenerative diseases Author(s): Lee, Sung Bae Abstract: With increasing life expectancy, neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Amyotrophic Lateral Sclerosis (ALS) and Huntington’s disease (HD), have become one of the major threats to humans. Although the symptoms vary depending on the type of disease, these neurodegenerative diseases share protein toxicity as one of their key pathogenic mechanisms. Herein protein toxicity is defined as all the pathological changes that ensue from accumulation, mis-localization and/or oligomerization of disease-associated toxic proteins such as α-synuclein in PD, polyglutamine (polyQ)-containing proteins in polyQ diseases (e.g., HD), and SOD1 and TDP-43 in ALS. Protein toxicity in affected neurons encompasses a number of cellular defects, such as mitochondrial dysfunction, impaired protein/RNA quality control, and neuronal cell death, all of which critically contribute to the initiation and progression of the diseases. Thus, strengthening our understanding of the nature of protein toxicity is essential for the development of effective therapeutics for these diseases. In this talk, I will present our current understanding on the molecular and cellular mechanisms of protein toxicity in neurodegenerative diseases, particularly in the context of polyglutamine (polyQ) diseases, based on our ongoing studies. Key words: Early neuropathy, neurodegenerative diseases, protein toxicity

2018-08-08T15:00:00Z Lee, Sung-Bae https://scholar.dgist.ac.kr/handle/20.500.11750/14663 2025-07-25T04:07:58Z 2018-11-07T15:00:00Z

Title: The mechanisms of protein toxicity in neurodegenerative diseases Author(s): Lee, Sung-Bae Abstract: With increasing life expectancy, neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Amyotrophic Lateral Sclerosis (ALS) and Huntington’s disease (HD), have become one of the major threats to humans. Although the symptoms vary depending on the type of disease, these neurodegenerative diseases share protein toxicity as one of their key pathogenic mechanisms. Herein protein toxicity is defined as all the pathological changes that ensue from accumulation, mis-localization and/or oligomerization of disease-associated toxic proteins such as α-synuclein in PD, polyglutamine (polyQ)-containing proteins in polyQ diseases (e.g., HD), and SOD1 and TDP-43 in ALS. Protein toxicity in affected neurons encompasses a number of cellular defects, such as mitochondrial dysfunction, impaired protein/RNA quality control, and neuronal cell death, all of which critically contribute to the initiation and progression of the diseases. Thus, strengthening our understanding of the nature of protein toxicity is essential for the development of effective therapeutics for these diseases. In this talk, I will present our current understanding on the molecular and cellular mechanisms of protein toxicity in neurodegenerative diseases, particularly in the context of polyglutamine (polyQ) diseases, based on our ongoing studies.

2018-11-07T15:00:00Z Kim, Yoon Ha Kim, EunSeon Chung, Chang Geon Lee, Sung-Bae https://scholar.dgist.ac.kr/handle/20.500.11750/14437 2025-07-25T03:22:52Z 2019-06-02T15:00:00Z

Title: Increased accumulation of Staufen in nucleus contributes to C9ALS/FTD pathology Author(s): Kim, Yoon Ha; Kim, EunSeon; Chung, Chang Geon; Lee, Sung-Bae Abstract: G4C2 repeat expansion mutation of C9orf72 is the most common cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). RNA G4C2 repeats produce 5 dipeptide repeat (DPR) proteins via repeat-associated non-ATG translation. Arginine-rich DPR proteins such as polyGly-Arg (GR) and polyPro-Arg (PR) are highly toxic and can perturb the dynamics and functions of various RNA binding proteins (RBPs). Recently, Staufen, a double-stranded RNA binding protein, was identified as one of the top interactors of poly (GR) and poly (PR), but the way in which Staufen mediates toxicity is currently unknown. Here, we show that poly (GR) and poly (PR) cause RNA-dependent nuclear accumulation of Staufen. Taken together, these data suggest that nuclear accumulation of Staufen may contribute to C9ALS/FTD pathogenesis.

2019-06-02T15:00:00Z 김경민 정창근 권민지 박정향 차인준 조재호 한명훈 박성순 김은선 고병수 이다빈 정연진 Lee, Sung-Bae https://scholar.dgist.ac.kr/handle/20.500.11750/14411 2025-07-25T03:25:27Z 2019-06-23T15:00:00Z

Title: Screening platform for assessing cellular and behavioral defects in Drosophila Melanogaster Author(s): 김경민; 정창근; 권민지; 박정향; 차인준; 조재호; 한명훈; 박성순; 김은선; 고병수; 이다빈; 정연진; Lee, Sung-Bae Abstract: For screening drugs or molecules that can modify disease pathophysiology of human disease or conduct drug screening, the use of appropriate in vivo model with low expenditure suitable for large-scale screening is essential. Drosophila Melanogaster, whose genome contain orthologs for 75% of human disease-related genes, offers a quantitative screening platform for assessing both cellular and behavioral defects that are thought to be representative of human diseases like Parkinson’s disease(PD), Huntington’s disease(HD) or amyotrophic lateral sclerosis(ALS). Here, we present the low cost screening analysis platform available for measuring cellular and behavioral defects in Drosophila. This platform can be adapted for the use of therapeutic target discovery process as an economic and powerful in vivo screening tool for the researchers.

2019-06-23T15:00:00Z