A Correlative Study on Amyloid-β Variants Exhibit Different Cytotoxicities Depending on Ratio of Aβ40 to Aβ42 and Their Interaction Time and Implication of Aβ40 as a Primary Determinant for the Variable Cytotoxicities in Wild-type, Flemish and Dutch
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- 발행기관
- 조선대학교 기초과학연구원 바로가기
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- 간행물
- 통합자연과학논문집(구 조선자연과학논문집) KCI 등재 바로가기
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- 통권
- 제6권 1호 (2013.03)바로가기
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- 페이지
- pp.21-33
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- 저자
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- 언어
- 영어(ENG)
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- URL
- https://www.earticle.net/Article/A196749
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원문정보
초록
- 영어
- Formation of amyloid-β (Aβ) aggregates is a core process in the pathogenesis of Alzheimer’s disease. Importance of interaction of the length variants, Aβ42 and Aβ40 in the process and consequent cytotoxicity has been pointed out for wild-type Aβ previously. In addition to confirming the findings, the current study demonstrates that the potential interaction is also important for cytotoxicity of the Flemish and Dutch sequence variants. The interaction could strengthen or inhibit cytotoxicity of Aβ42/Aβ40 mixture, depending on interaction time of the length variants as well as the ratio and amyloidogenic property. The inhibitory effect was prominent at the early stage of aggregate formation in less amyloidogenic Flemish Aβ42/Aβ40 mixture, while strengthened cytotoxicity was exhibited at the stage in potently amyloidogenic Dutch variant and at the later stage in wild-type and the Flemish variant. The samples showing relatively robust cytotoxicity were those enriched in Aβ protofibril-like structures, implying strong correlation of the structure with cytotoxicity. The different consequence of the interaction on sequence variants is likely due to differential amyloidogenic property of each Aβ40 variant, rather than that of Aβ42, because aggregation rates and levels of Aβ40 variants are greatly variable depending on the sequence, compared to Aβ42 variants. These studies may highlight a potential role of Aβ40 in the cytotoxicity, providing a novel mechanistic insight into the pathogenesis of each FAD-associated variant.
목차
Abstract
1. Introduction
2. Experimental Section
2.1. Preparation of Aβ42
2.2. Cell Culture and Cytotoxicity Assay
2.3. Thioflavin (ThT) Binding Assay
2.4. Transmission Electron Microscopy (TEM)
2.5. Detection of Aβ Structural Species by Immunoblotting Assay
3. Results
3.1. Preparation of Aβ Peptides
3.2. Cytotoxic and Amyloidogenic Properties of Aβ Vary More in the Length Variants than in Sequence Variants
3.3. Aggregates Formation in Aβ42/Aβ40 Mixture Varies Depending on Its Ratio, Iinteraction Time and Amyloidogenic Property
3.4. Cell Death Induced by Concurrent Treatment of Aβ40 and 42 Varies Depending on the Ratio, Interaction Time and Amyloidogeni
3.5. Electron Micrographs of Aβ Assemblies Formed at Different Incubation Time
3.6. Level of Large (100 kDa) Oligomeric Species(LOS) of Aβ Peptide in the Aβ42/Aβ40 Mixture Correlates with Degree of Cytotoxi
4. Discussion
References
키워드
Aβ Flemish Dutch Ratio Interaction Cytotoxicity Alzheimer’s Disease저자
간행물 정보
발행기관
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- 발행기관명
- 조선대학교 기초과학연구원 [The Natural Science Research Institute of Chosun]
- 설립연도
- 2008
- 분야
- 자연과학>자연과학일반
- 소개
- 본 연구원은 기초과학을 진흥하기 위한 연구·교육 및 그 보급을 목적으로 한다. 이 목적을 달성하기 위하여 다음 각 호의 사업을 수행한다. 1. 기초과학 제 분야에 관한 조사와 연구 2. 기초과학에 관한 학술행사(학술대회, 학술세미나, 심포지엄, 초청강연회 등) 개최 3. 학문후속세대 및 일반인을 위한 기초과학 교육 4. 기관지『조선자연과학논문지』 발간 5. 『자연과학연구총서』, 『자연과학번역총서』 등 단행본 발간 6. 기타 본 연구원의 목적과 관련된 사업
간행물
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- 간행물명
- 통합자연과학논문집(구 조선자연과학논문집) [Journal of Integrative Natural Science]
- 간기
- 계간
- pISSN
- 2005-1042
- 수록기간
- 2008~2026
- 등재여부
- KCI 등재
- 십진분류
- KDC 405 DDC 505
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