| Autor: |
Pham DQH; Institute of Physics , Polish Academy of Sciences , Al. Lotnikow 32/46 , 02-668 Warsaw , Poland.; Institute for Computational Science and Technology , 6 Quarter, Linh Trung Ward, Thu Duc District, Ho Chi Minh City 700000 , Vietnam., Li MS; Institute of Physics , Polish Academy of Sciences , Al. Lotnikow 32/46 , 02-668 Warsaw , Poland., La Penna G; National Research Council Italy (CNR), Institute for Chemistry of Organometallic Compounds (ICCOM) , 50019 Florence , Italy.; Italian Institute for Nuclear Physics (INFN), Section of Roma-Tor Vergata , Rome 00133 , Italy. |
| Jazyk: |
angličtina |
| Zdroj: |
The journal of physical chemistry. B [J Phys Chem B] 2018 Jul 26; Vol. 122 (29), pp. 7243-7252. Date of Electronic Publication: 2018 Jul 17. |
| DOI: |
10.1021/acs.jpcb.8b03983 |
| Abstrakt: |
Amyloid-β (Aβ) peptides are intrinsically disordered peptides, and their aggregation is the hallmark of Alzheimer's disease development. The propensity of the Aβ peptide to intermolecular interactions, the latter favoring different types of oligomers and aggregated forms, has been the object of a huge number of studies. Several facts are now established: the presence of large amount of d-block (M) ions (Zn, Cu, and Fe) in the aggregated forms; the 1:1 M/Aβ ratio favors the formation of amorphous aggregates, with an aggregation rate lower than that in the absence of such ions. In particular, statistical models describing the interactions between copper and amyloid peptides are mandatory to explain the relationship between neurodegeneration, copper dyshomeostasis, and overproduction of reactive oxygen species, the latter event occurring with aging. In this work, we show, by replica-exchange molecular dynamics simulations, that a copper ion (Cu 2+ ) bound as in the experimentally observed prevailing coordination enhances the probability of closed structures that hinder the formation of extended intermolecular hydrogen bonds that stabilize fibrillar ordered aggregated forms. On the other hand, this effect enhances the catalytic role of the complex during the lifetime of soluble forms. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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