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Inhibition of CDK4/6 regulates AD pathology, neuroinflammation and cognitive function through DYRK1A/STAT3 signaling
Blocking CDK4/6 may influence Alzheimer's-related brain changes, inflammation, and thinking by affecting DYRK1A/STAT3 signaling
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Abstract
Abemaciclib mesylate improved spatial and recognition memory in 5xFAD mice, an Alzheimer's disease model.
- Abemaciclib mesylate regulated dendritic spine number and neuroinflammatory responses in 5xFAD mice.
- The drug inhibited Aβ accumulation by enhancing the activity of the Aβ-degrading enzyme neprilysin and the α-secretase ADAM17.
- It decreased the protein level of the γ-secretase PS-1 in both young and aged 5xFAD mice.
- Abemaciclib mesylate suppressed tau phosphorylation by reducing levels of DYRK1A and/or p-GSK3β in 5xFAD and tau-overexpressing PS19 mice.
- In wild-type mice injected with lipopolysaccharide, the drug restored spatial and recognition memory and reduced microglial/astrocytic activation.
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