Chronic low dose of AM404 ameliorates the cognitive impairment and pathological features in hyperglycemic 3xTg-AD mice.

ABSTRACT:

Rationale

Hyperglycemia accelerates the progression of Alzheimer's disease (AD), and GSK3β plays a potential link between AD and hyperglycemia. Therefore, a direct or indirect GSK3β inhibition may have potential to delay the progression of AD. Our previous biochemical assay identified AM404 as a GSK3β inhibitor at high dose (IC50 = 5.353 μM); however, other study suggests that AM404 impaired synaptic plasticity of hippocampus at high dose (10 mg/kg; i.p.). Therefore, the dose and duration of treatment are crucial for the effects of AM404.

Objective

The effects and molecular mechanisms of AM404 at low dose were evaluated from in vitro to in vivo models.

Methods

AM404 (0.1-0.5 μM) was tested on tau hyperphosphorylated mouse hippocampal primary cultures treated with Wort

SUBMITTER: Huang HJ 

PROVIDER: S-EPMC6469654 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature