Role of the carboxy groups of triterpenoids in their inhibition of the nucleation of amyloid β42 required for forming toxic oligomers

Herein we report that a preferable inhibition of the nucleation phase of Aβ42, related to the formation of toxic oligomers, by triterpenoids from medicinal herbs originates from a salt bridge of their carboxy groups with Lys16 and 28 in Aβ42. Such a direct interaction targeting the monomer, dimer, a...

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Bibliographic Details
Published in:Chemical communications (Cambridge, England) England), 2018-06, Vol.54 (49), p.6272-6275
Main Authors: Murakami, Kazuma, Yoshioka, Takuya, Horii, Shiori, Hanaki, Mizuho, Midorikawa, Satohiro, Taniwaki, Shinji, Gunji, Hiroki, Akagi, Ken-ichi, Kawase, Taiji, Hirose, Kenji, Irie, Kazuhiro
Format: Article
Language:English
Subjects:
Congeners
Dimers
Medicinal herbs
Nucleation
Oligomerization
Oligomers
Trimers
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Summary:Herein we report that a preferable inhibition of the nucleation phase of Aβ42, related to the formation of toxic oligomers, by triterpenoids from medicinal herbs originates from a salt bridge of their carboxy groups with Lys16 and 28 in Aβ42. Such a direct interaction targeting the monomer, dimer, and trimer suppressed further oligomerization. In contrast, the corresponding congeners without carboxy groups failed to do so. The carboxy group of ursane-type triterpenoids plays a critical role in the suppression of toxic Aβ42 nucleation by targeting the monomer to trimer.
ISSN:1359-7345
1364-548X
DOI:10.1039/c8cc03230k