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A guanidine-appended scyllo-inositol derivative AAD-66 enhances brain delivery and ameliorates Alzheimer's phenotypes.

TitleA guanidine-appended scyllo-inositol derivative AAD-66 enhances brain delivery and ameliorates Alzheimer's phenotypes.
Publication TypeJournal Article
Year of Publication2017
AuthorsLee D, Lee W-S, Lim S, Kim YKyung, Jung H-Y, Das S, Lee J, Luo W, Kim K-T, Chung S-K
JournalSci Rep
Volume7
Issue1
Pagination14125
Date Published2017 Oct 26
ISSN2045-2322
Abstract

Alzheimer's disease (AD) is a degenerative brain disease that destroys memory and other important mental functions but lacks efficient therapeutic agents. Blocking toxic amyloid β (Aβ) could be beneficial for AD and represents a promising therapeutic strategy for AD treatment. scyllo-Inositol (SI) is a potential therapeutic for AD by directly interacting with the Aβ peptide to inhibit Aβ42 fiber formation. Clinical studies of SI showed promising benefits on mild to moderate AD, however, with limitations on dosage regime. A new strategy to enhance the brain delivery of SI is needed to achieve the efficacy with minimum adverse effects. Herein, we report that a novel guanidine-appended SI derivative AAD-66 resulted in more effective reductions of brain Aβ and plaque deposits, gliosis, and behavioral memory deficits in the disease-established 5xFAD mice. Overall, our present study reveals the potential of AAD-66 as a promising therapeutic agent for AD.

DOI10.1038/s41598-017-14559-7
Alternate JournalSci Rep
PubMed ID29074878
PubMed Central IDPMC5658413