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Amyloid-β protein hexamers induced neuritic degeneration and neurotoxicity in the mouse hippocampal neurons : 마우스 해마 신경세포에서 신경돌기 퇴화 및 신경독성을 일으키는 육합체 Aβ 단백질의 효과
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | 성노현 | - |
dc.contributor.author | 이유민 | - |
dc.date.accessioned | 2017-10-31T08:31:57Z | - |
dc.date.available | 2020-10-06T08:30:52Z | - |
dc.date.issued | 2017-08 | - |
dc.identifier.other | 000000145978 | - |
dc.identifier.uri | https://hdl.handle.net/10371/138069 | - |
dc.description | 학위논문 (석사)-- 서울대학교 대학원 자연과학대학 생명과학부, 2017. 8. 성노현. | - |
dc.description.abstract | Alzheimers disease (AD) has become one of the greatest threat to
global well-being and economy. Despite the fact that about 46.8 million people worldwide are currently affected by the disease and this number is expected to be tripled by 2050, there is currently no treatment available to halt the progression of disease despite many years of extensive research. Early reports stated amyloid fibrils were the cause of AD, but the recent research have found that soluble beta-amyloid (Aβ) oligomers are key pathological agents which are responsible for initiating a complex cascade that ultimately results in AD. However, the precise mechanism underlying AD is still unclear, and this is partly due to the unresolved nature of Aβ conformations that exert neurotoxicity and the difficulty of preparing the oligomers due to their thermodynamic instability. Here, we developed a novel method to prepare Aβ oligomers that stably maintain each oligomeric state from dimer to hexamer, respectively. We constructed the expression vectors to express Aβ and fused proteins that have been reported to form oligomers in a stable manner (leading proteins) at its N-terminus. We expect, in this way, this would help inducing a stable formation of each form of Aβ oligomers. With this method, we prepared leading proteins, Aβ1-40 and Aβ1-42 present in each of five different oligomeric state. The mouse hippocampal neurons treated with hexameric Aβ1-42 exhibited a severely disrupted morphology, suggesting the Aβ1-42 hexamers, but not other types of oligomers, play a key role in AD pathogenesis. We concluded that Aβ1-42 hexamers are neurotoxic species, stressing the importance of the hexamer as a potential target in development of AD immunotherapy. | - |
dc.description.tableofcontents | Introduction 1
A. Alzheimers Disease (AD) 1 B. Familial/Sporadic forms of AD 2 C. Processing of amyloid precursor proteins (APP) 3 D. Amyloid cascade hypothesis 5 E. Current treatment for AD 5 Materials and Methods 7 A. Construction of expression vectors 7 B. Protein expression and purification 7 C. Western blotting and Coomassie blue staining 8 D. Establishment of primary mouse neuron cultures 8 Results 42 A. Generation of expression vectors that induce formation of soluble Aβ1-40 and Aβ1-42 oligomers from dimer to hexamer 9 B. Formation of oligomers at five different oligomeric states 14 C. Validated use of leading proteins as control proteins 14 D. Neurotoxic effects of Aβ1-42 Hexamers 19 E. Non-neurotoxic effects of Aβ1-40 oligomers 20 Discussion 26 References 30 Korean abstract 39 | - |
dc.format | application/pdf | - |
dc.format.extent | 859917 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | Alzheimer’s diesase | - |
dc.subject | beta-amyloid | - |
dc.subject | oligomers | - |
dc.subject | neurotoxicity | - |
dc.subject | immunotherapy | - |
dc.subject.ddc | 570 | - |
dc.title | Amyloid-β protein hexamers induced neuritic degeneration and neurotoxicity in the mouse hippocampal neurons | - |
dc.title.alternative | 마우스 해마 신경세포에서 신경돌기 퇴화 및 신경독성을 일으키는 육합체 Aβ 단백질의 효과 | - |
dc.type | Thesis | - |
dc.description.degree | Master | - |
dc.contributor.affiliation | 자연과학대학 생명과학부 | - |
dc.date.awarded | 2017-08 | - |
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