자료유형  

 학위논문

Control Number  

0017165111

International Standard Book Number  

9798346859628

Dewey Decimal Classification Number  

574

Main Entry-Personal Name  

Cheng, Xinyi.

Publication, Distribution, etc. (Imprint  

[S.l.] : University of California, Los Angeles., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

220 p.

General Note  

Source: Dissertations Abstracts International, Volume: 86-06, Section: B.

General Note  

Advisor: Eisenberg, David S.

Dissertation Note  

Thesis (Ph.D.)--University of California, Los Angeles, 2024.

Summary, Etc.  

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.

Subject Added Entry-Topical Term  

Biochemistry.

Subject Added Entry-Topical Term  

Microbiology.

Subject Added Entry-Topical Term  

Neurosciences.

Subject Added Entry-Topical Term  

Molecular biology.

Index Term-Uncontrolled  

Alzheimer's disease

Index Term-Uncontrolled  

Cryogenic electron microscopy

Index Term-Uncontrolled  

Neurodegeneration

Index Term-Uncontrolled  

Structural biology

Index Term-Uncontrolled  

Tauopathies

Added Entry-Corporate Name  

University of California, Los Angeles Molecular Biology 0573

Host Item Entry  

Dissertations Abstracts International. 86-06B.

Electronic Location and Access  

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Control Number  

joongbu:657754