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Home > Multifunctional Compound AD-35 Improves Cognitive Impairment and Attenuates the Production of TNF-α and IL-1β in an Aβ25-35-induced Rat Model of Alzheimer's Disease.

TitleMultifunctional Compound AD-35 Improves Cognitive Impairment and Attenuates the Production of TNF-α and IL-1β in an Aβ25-35-induced Rat Model of Alzheimer's Disease.
Publication TypeJournal Article
Year of Publication2017
AuthorsLi, L, Xu, S, Liu, L, Feng, R, Gong, Y, Zhao, X, Li, J, Cai, J, Feng, N, Wang, L, Wang, X, Peng, Y
JournalJ Alzheimers Dis
Volume56
Issue4
Pagination1403-1417
Date Published2017
ISSN1875-8908
Abstract

The dyshomeostasis of transition metal ions, accumulation of amyloid-β (Aβ) senile plaques and neuroinflammatory response found in the brain of patients with Alzheimer's disease (AD) have been suggested to be involved in AD pathogenesis. Novel compounds capable of targeting metal-Aβ species and neuroinflammation would be valuable. AD-35 is such a patented small-molecule compound derived from innovative modification of the chemical structure of donepezil. This compound could moderately inhibit acetylcholinesterase and metal-induced Aβ aggregation in vitro and showed disassembly of Aβ aggregates. The effects of AD-35 on cognitive impairments and neuroinflammatory changes caused by intracerebroventricular injection of Aβ25-35 were studied in rats. Compared to sham group, Aβ25-35 injection significantly led to learning and memory deficits, astrocyte activation, and pro-inflammatory cytokines releases (TNF-α and IL-1β). Further studies indicated that the phosphorylation of extracellular signal-regulated kinase was involved in astrocyte activation and pro-inflammatory cytokines production. Oral administration of AD-35 could markedly attenuate Aβ25-35 injection-induced astrocyte activation, pro-inflammatory cytokines TNF-α and IL-1β release, and memory deficits. On the contrary, donepezil only showed inhibition of IL-1β production, but failed to block astrocyte activation and TNF-α production. These results showed that AD-35 would be a novel multi-mechanism drug for the prevention and/or treatment of AD.

DOI10.3233/JAD-160587
Alternate JournalJ. Alzheimers Dis.
PubMed ID28157092
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