Artemisinin alleviates astrocyte overactivation and neuroinflammation by modulating the IRE1/NF-κB signaling pathway in in vitro and in vivo Alzheimer's disease models

Jan 18, 2025Free radical biology & medicine

Artemisinin reduces brain support cell overactivity and inflammation by affecting a key cell stress and immune pathway in Alzheimer's disease models

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Abstract

Artemisinin (ART) improved cognitive function and reduced astrocyte overactivation in 3 × Tg-AD mice.

  • Neuroinflammation and heightened glial activity, particularly astrocyte overactivation, are associated with Alzheimer's disease.
  • ART attenuated amyloid-beta (Aβ)-induced astrocyte activation, endoplasmic reticulum (ER) stress, and inflammatory responses in cell cultures.
  • The effects of ART were linked to the inhibition of IRE1 phosphorylation and the NF-κB pathway.
  • ART restored neurotrophic function of astrocytes in co-cultured neurons, preventing neuronal apoptosis during Aβ treatment.
  • In AD mice, ART treatment reduced neuroinflammation, ER stress, and neuronal apoptosis while improving cognitive function.
  • Overexpression of IRE1 in astrocytes negated the beneficial effects of ART in the context of Alzheimer's disease.

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