| First Author | Tan X | Year | 2021 |
| Journal | Behav Brain Res | Volume | 398 |
| Pages | 112968 | PubMed ID | 33069740 |
| Mgi Jnum | J:311260 | Mgi Id | MGI:6709630 |
| Doi | 10.1016/j.bbr.2020.112968 | Citation | Tan X, et al. (2021) Isoorientin, a GSK-3beta inhibitor, rescues synaptic dysfunction, spatial memory deficits and attenuates pathological progression in APP/PS1 model mice. Behav Brain Res 398:112968 |
| abstractText | beta-Amyloid (Abeta) elevation, tau hyperphosphorylation, and neuroinflammation are major hallmarks of Alzheimer's disease (AD). Glycogen synthase kinase-3beta (GSK-3beta) is a key protein kinase implicated in the pathogenesis of AD. Blockade of GSK-3beta is an attractive therapeutic strategy for AD. Isoorientin, a 6-C-glycosylflavone, was previously shown to be a highly selective inhibitor of GSK-3beta, while exerting neuroprotective effects in neuronal models of AD. In the present study, we evaluated the in vivo effects of isoorientin on GSK-3beta, tau phosphorylation, Abeta 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-3beta overactivation, tau hyperphosphorylation, Abeta deposition, and neuroinflammation. For neuroinflammation, isoorientin treatment reduced the number of activated microglia associated with Abeta-positive plaques, and in parallel reduced the levels of pro-inflammatory factors in the brains of APP/PS1 mice. Strikingly, isoorientin reversed deficits in synaptic long-term potentiation and spatial memory relevant to cognitive functions. Together, the findings suggest that isoorientin is a brain neuroprotector and may be a promising drug lead for treatment of AD and related neurodegenerative disorders. |
