Isoorientin, a GSK-3 β inhibitor, rescues synaptic dysfunction, spatial memory deficits and attenuates pathological progression in APP/PS1 model mice.

Isoorientin, a GSK-3β inhibitor, rescues synaptic dysfunction, spatial memory deficits and attenuates pathological progression in APP/PS1 model mice. Behav Brain Res. 2020 Oct 15;:112968 Authors: Tan X, Liang Z, Li Y, Zhi Y, Yi L, Bai S, Forest KH, Nichols RA, Dong Y, Li QX Abstract β-Amyloid (Aβ) elevation, tau hyperphosphorylation, and neuroinflammation are major hallmarks of Alzheimer's disease (AD). Glycogen synthase kinase-3β (GSK-3β) is a key protein kinase implicated in the pathogenesis of AD. Blockade of GSK-3β is an attractive therapeutic strategy for AD. Isoorientin, a 6-C-glycosylflavone, was previously shown to be a highly selective inhibitor of GSK-3β, while exerting neuroprotective effects in neuronal models of AD. In the present study, we evaluated the in vivo effects of isoorientin on GSK-3β, tau phosphorylation, Aβ deposition, neuroinflammatory response, long-term potentiation, and spatial memory in amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice using biochemical, electrophysiological, and behavioral tests. Chronic oral administration of isoorientin to APP/PS1 mice at 8 months of age attenuated multiple AD pathogenic hallmarks in the brains, including GSK-3β overactivation, tau hyperphosphorylation, Aβ deposition, and neuroinflammation. For neuroinflammation, isoorientin treatment reduced the number of activated microglia associated with Aβ-positive plaques, and in parallel reduced the l...
Source: Behavioural Brain Research - Category: Neurology Authors: Tags: Behav Brain Res Source Type: research
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