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

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자연과학대학 생명과학부
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서울대학교 대학원
Alzheimer’s diesasebeta-amyloidoligomersneurotoxicityimmunotherapy
학위논문 (석사)-- 서울대학교 대학원 자연과학대학 생명과학부, 2017. 8. 성노현.
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

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.
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College of Natural Sciences (자연과학대학)Dept. of Biological Sciences (생명과학부)Theses (Master's Degree_생명과학부)
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