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| Type |
Poster Presentation |
| Area |
Inorganic Chemistry |
| Room No. |
Grand Ballroom |
| Time |
10월 19일 (금요일) 11:00~12:30 |
| Code |
INOR.P-63 |
| Subject |
Molecular-Level Studies of Amyloid-β and Proteins:
Interactions with and without Metal Ions and Aggregation |
| Authors |
Hyuck Jin Lee, Tae Su Choi1, Masha G. Savelieff2, Megan Brunjes Brophy3, Toshiki G. Nakashige3, Elizabeth M. Nolan3,*, Hugh I. Kim1,*, Mi Hee Lim4,*
Korea Advanced Institute of Science and Technology, Korea
1Department of Chemistry, Korea University, Korea
2SciGency Science Communications, U.S.A., United States
3Department of Chemistry, Massachusetts Institute of Technology (MIT), United States
4Department of Chemistry, Korea Advanced Institute of Science and Technology, Korea
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| Abstract |
Deposition of misfolded protein aggregates, such as senile plaques composed of amyloid-β (Aβ) aggregates, is a characteristic feature of Alzheimer’s disease (AD).1,2 Due to this hallmark of the disease and toxicity associated with Aβ aggregates, previous studies have focused on understanding and modulating Aβ aggregation pathways. In the brain, the aggregation of Aβ could be affected by (i) metal ions, such as Zn(II) and Cu(II), which are observed to bind to Aβ and accelerate its aggregation; (ii) proteins which could interact with Aβ [e.g., human serum albumin (HSA; the most abundant plasma protein)] or (iii) be overexpressed and possibly co-localized with Aβ aggregates in the AD-affected brain [e.g., S100A8 and S100A9 which exist as heterodimeric form of S100A8/S100A9, called calprotectin (CP)]. HSA and S100A9 have been suggested to suppress and facilitate the aggregation of metal-free Aβ, respectively;3,4 however, the information on their interactions with metal-free Aβ has been still limited. In addition, although HSA and CP can interact with metal ions, their direct interaction and influence on the aggregation pathways and toxicity of metal-associated Aβ have been rarely reported. In this presentation, we will present the ability of HSA and CP to modulate the aggregation of Aβ with and without metal ions possibly through direct interaction with Aβ. HSA and CP could form complexes with Aβ peptides, alter their aggregation pathways, and affect the toxicity induced by metal-free and metal-bound Aβ to different degrees. Our overall investigations demonstrate a potential network among Aβ, protein(s), and metal ions related to the pathogenesis of AD.5,6
References
1. Savelieff, M. G.; Nam, G.; Kang, J.; Lee, H. J.; Lee, M.; Lim, M. H. Chem. Rev. 2018, DOI: 10.1021/acs.chemrev.8b00138.
2. Lee, S. J. C.; Nam, E.; Lee, H. J.; Savelieff, M. G.; Lim, M. H. Chem. Soc. Rev. 2017, 46, 310-323.
3. Milojevic, J.; Costa, M.; Ortiz, A. M.; Jorquera, J. I.; Melacini, G. J. Alzheimers Dis. 2014, 38, 753-765.
4. Zhang, C.; Liu, Y.; Gilthorpe, J.; van der Maarel, J. R. C. PLoS One, 2012, 7, e32953.
5. Lee, H. J.;§ Savelieff, M. G.;§ Kang, J.; Brophy, M. B.; Nakashige, T. G.; Lee, S. J. C.; Nolan, E. M.; Lim, M. H. Metallomics 2018, 10, 1116-1127 (§co-first authorship).
6. Choi, T. S.;§ Lee, H. J.;§ Han, J. Y.; Lim, M. H.; Kim, H. I. J. Am. Chem. Soc. 2017, 139, 15437-15445 (§co-first authorship). |
| E-mail |
hyuckjin@kaist.ac.kr |
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122nd General Meeting of the KCS