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Structure-Based Investigation Into Neurodegenerative Disease-Causing Amyloid Protein Fibrils
Structure-Based Investigation Into Neurodegenerative Disease-Causing Amyloid Protein Fibrils
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211153125
- ISBN
- 9798346859628
- DDC
- 574
- 저자명
- Cheng, Xinyi.
- 서명/저자
- Structure-Based Investigation Into Neurodegenerative Disease-Causing Amyloid Protein Fibrils
- 발행사항
- [Sl] : University of California, Los Angeles, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 220 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-06, Section: B.
- 주기사항
- Advisor: Eisenberg, David S.
- 학위논문주기
- Thesis (Ph.D.)--University of California, Los Angeles, 2024.
- 초록/해제
- 요약Amyloid proteins are widely prevalent both in normal biology and in disease. This curious protein folding phenomenon, into closely packed cross-β folds, has captivated scientists. Specifically, amyloid proteins are linked to a lot of neurodegeneration diseases, like amyloid β and tau in Alzheimer's disease's, TDP-43 in ALS and so on. Recently, with the advancement of structural biology techniques like cryogenic electron microscopy (cryoEM), we can finally visualize the atomic structure of such amyloid assemblies extracted directly from patients. Curiously, amyloid fibrils of the same protein would take on distinctive structures unique to a particular disease. This phenomenon is observed with tau protein in various tauopathies, and TDP-43 protein in various subtypes of FTLD-TDP. On the other hand, these proteins often take on heterogeneous amyloid structures in vivo that are completely different from pathological structures. With this knowledge in mind, more studies for diagnostics and therapeutics are conducted on patient-derived materials to preserve the pathological disease structures. In turn, a lot of studies into pathological amyloids in neurodegeneration has entered an era of "structure-based" research. Diagnostics like PET-tracers, therapeutics like small molecule drugs, and other research tools such as antibodies and cell lines all need to be designed with the target structure in mind. In this collection of thesis works, I investigated an antibody that seems to be specific for a particular amyloid structure formed by the protein tau. It is the first known antibody that can distinguish not aggregated protein from monomers, but also differentiates between different amyloid structures formed by the same protein. I also assisted in solving the first structure of an amyloid fibril bound with a small molecule disaggregant, and using insight from this structure continued to design and test small molecule disaggregants specifically targeted towards tau in the AD amyloid fold. Aside from tau, I also worked on TDP-43 and studied the structural landscape of TDP-43 in various diseases such as FTLD and ALS using a cell-based model. Overall, my work exemplifies the new frontier of structure-based amyloid research into neurodegeneration and showcases investigation into antibodies, small molecule disaggregants and cell models in the context of the ever-changing landscape of amyloid structures.
- 일반주제명
- Biochemistry
- 일반주제명
- Microbiology
- 일반주제명
- Neurosciences
- 일반주제명
- Molecular biology
- 키워드
- Tauopathies
- 기타저자
- University of California, Los Angeles Molecular Biology 0573
- 기본자료저록
- Dissertations Abstracts International. 86-06B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■00520250211153125
■006m o d
■007cr#unu||||||||
■020 ▼a9798346859628
■035 ▼a(MiAaPQ)AAI31764629
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aCheng, Xinyi.
■24510▼aStructure-Based Investigation Into Neurodegenerative Disease-Causing Amyloid Protein Fibrils
■260 ▼a[Sl]▼bUniversity of California, Los Angeles▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a220 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-06, Section: B.
■500 ▼aAdvisor: Eisenberg, David S.
■5021 ▼aThesis (Ph.D.)--University of California, Los Angeles, 2024.
■520 ▼aAmyloid proteins are widely prevalent both in normal biology and in disease. This curious protein folding phenomenon, into closely packed cross-β folds, has captivated scientists. Specifically, amyloid proteins are linked to a lot of neurodegeneration diseases, like amyloid β and tau in Alzheimer's disease's, TDP-43 in ALS and so on. Recently, with the advancement of structural biology techniques like cryogenic electron microscopy (cryoEM), we can finally visualize the atomic structure of such amyloid assemblies extracted directly from patients. Curiously, amyloid fibrils of the same protein would take on distinctive structures unique to a particular disease. This phenomenon is observed with tau protein in various tauopathies, and TDP-43 protein in various subtypes of FTLD-TDP. On the other hand, these proteins often take on heterogeneous amyloid structures in vivo that are completely different from pathological structures. With this knowledge in mind, more studies for diagnostics and therapeutics are conducted on patient-derived materials to preserve the pathological disease structures. In turn, a lot of studies into pathological amyloids in neurodegeneration has entered an era of "structure-based" research. Diagnostics like PET-tracers, therapeutics like small molecule drugs, and other research tools such as antibodies and cell lines all need to be designed with the target structure in mind. In this collection of thesis works, I investigated an antibody that seems to be specific for a particular amyloid structure formed by the protein tau. It is the first known antibody that can distinguish not aggregated protein from monomers, but also differentiates between different amyloid structures formed by the same protein. I also assisted in solving the first structure of an amyloid fibril bound with a small molecule disaggregant, and using insight from this structure continued to design and test small molecule disaggregants specifically targeted towards tau in the AD amyloid fold. Aside from tau, I also worked on TDP-43 and studied the structural landscape of TDP-43 in various diseases such as FTLD and ALS using a cell-based model. Overall, my work exemplifies the new frontier of structure-based amyloid research into neurodegeneration and showcases investigation into antibodies, small molecule disaggregants and cell models in the context of the ever-changing landscape of amyloid structures.
■590 ▼aSchool code: 0031.
■650 4▼aBiochemistry
■650 4▼aMicrobiology
■650 4▼aNeurosciences
■650 4▼aMolecular biology
■653 ▼aAlzheimer's disease
■653 ▼aCryogenic electron microscopy
■653 ▼aNeurodegeneration
■653 ▼aStructural biology
■653 ▼aTauopathies
■690 ▼a0487
■690 ▼a0410
■690 ▼a0317
■690 ▼a0307
■71020▼aUniversity of California, Los Angeles▼bMolecular Biology 0573.
■7730 ▼tDissertations Abstracts International▼g86-06B.
■790 ▼a0031
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17165111▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
