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

?-Amyloid (A?) elevation, tau hyperphosphorylation, and neuroinflammation are major hallmarks of Alzheimer’s disease (AD). Glycogen synthase kinase-3? (GSK-3?) is a key protein kinase implicated in the pathogenesis AD. Blockade GSK-3? an attractive therapeutic strategy for Isoorientin, 6-C-glycosylflavone, was previously shown to be highly selective inhibitor GSK-3?, while exerting neuroprotective effects neuronal models In present study, we evaluated vivo isoorientin on phosphorylation, A? deposition, neuroinflammatory response, long-term potentiation, spatial memory amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice using biochemical, electrophysiological, behavioral tests. Chronic oral administration APP/PS1 at 8 months age attenuated multiple AD pathogenic brains, including overactivation, neuroinflammation. For neuroinflammation, treatment reduced number activated microglia associated with A?-positive plaques, parallel levels pro-inflammatory factors brains mice. Strikingly, reversed deficits synaptic potentiation relevant cognitive functions. Together, findings suggest that brain neuroprotector may promising drug lead related neurodegenerative disorders.