The novel DYRK1A inhibitor KVN93 regulates cognitive function, amyloid-beta pathology, and neuroinflammation

Sep 8, 2020Free radical biology & medicine

The new DYRK1A blocker KVN93 may improve thinking, reduce amyloid-beta buildup, and lower brain inflammation

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Abstract

KVN93 treatment in 5x FAD mice significantly improved long-term memory and reduced Aβ plaque levels.

  • KVN93 enhanced dendritic synaptic function, which is associated with improved long-term memory.
  • Aβ plaque levels were significantly reduced by KVN93 through the regulation of Aβ degradation enzymes neprilysin and insulin-degrading enzyme.
  • Microglial and astrocyte activation induced by Aβ was significantly suppressed in KVN93-treated 5x FAD mice.
  • KVN93 altered neuroinflammation in microglial cells but not in primary astrocytes by modulating signaling pathways.
  • In wild-type mice, KVN93 treatment reduced activation of microglia and astrocytes following LPS injection.

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