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Glutamine-rich interactors of mutant huntingtin modulate neuronal toxicity by promoting cytoplasmic huntingtin aggregation

Title
Glutamine-rich interactors of mutant huntingtin modulate neuronal toxicity by promoting cytoplasmic huntingtin aggregation
Translated Title
독성 헌팅틴 단백질과 상호작용하는 글루타민 풍부 단백질의 세포질 헌팅틴 응집체 형성 촉진 및 신경세포 독성 조절 이해
Authors
In Jun Cha
DGIST Authors
In Jun Cha; Sung Bae Lee; Daehee Hwang
Advisor(s)
이성배
Co-Advisor(s)
Daehee Hwang
Issue Date
2021
Available Date
2022-07-07
Degree Date
2021/02
Type
Thesis
Keywords
Huntington’s disease, Huntingtin, Cytoplasmic aggregates, Neuronal toxicity, 헌팅턴씨 병, 헌팅틴 단백질, 세포질 응집체, 신경세포 독성
Table Of Contents
Ⅰ. INTRODUCTION 1 ⅠⅠ. MATERIALS AND METHODS 4 2-1. Fly stocks 4 2-2. Generation of transgenic fly lines 5 2-3. Microscope image acquisition 5 2-4. Immunostaining 6 2-5. Image processing and analyses 6 2-6. Rapid Iterative Negative Geotaxis (RING) assay 7 2-7. Separation of SDS–soluble and –insoluble fractions for Western blot analysis 7 2-8. Nuclear extraction 8 2-9. Western blot 8 2-10. Statistical analysis 9 2-11. Analysis of survival rate 9 2-12. Identification of Q-rich proteins 9 2-13. Calculation of co-localization score (CLS) 10 2-14. Calculation of cytoplasm to nucleus score (CNS) 10 2-15. Partial least square-discriminatory analysis (PLS-DA) 11 2-16. Functional enrichment analysis 12 2-17. Reconstruction of network model 13 ⅠⅠⅠ. RESULTS 14 3-1. Conversion of cytoplasmic mHtt to cleaved nuclear mHtt is critical for mHtt toxicity 14 3-2. Knockdown of strong mHtt interactors reduces cytoplasmic mHtt aggregates 25 3-3. Cytoplasmic localization and Q-richness are important for strong interaction with cytoplasmic mHtt proteins 46 3-4. In silico model predicts cytoskeletal regulators as strong interactors to modulate the amounts of cytoplasmic mHtt aggregates 56 3-5. Knockdown of strong mHtt interactors increases mHtt toxicity in neurons 62 ⅠV. DISCUSSION 74 V. REFERENCES 78 VI. SUMMARY IN KOREAN 88
URI
http://dgist.dcollection.net/common/orgView/200000363192
http://hdl.handle.net/20.500.11750/16676
DOI
10.22677/thesis.200000363192
Degree
Doctor
Department
Brain and Cognitive Sciences
University
DGIST
Related Researcher
  • Author Lee, Sung Bae Laboratory of Neurodegenerative Diseases and Aging
  • Research Interests Cellular mechanism of neurodegenerative diseases; Neuronal maintenance and remodeling; 퇴행성 뇌질환의 세포기전; 신경계 유지 및 리모델링 연구
Files:
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Collection:
Department of Brain SciencesThesesPh.D.


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