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Ganoderic Acid A Mitigates Sleep Deprivation-Induced Behavioral Deficits and Aging-like Phenotypes by Cryptochrome 1-Mediated Suppression of Ferroptosis and Pyroptosis
Ganoderic Acid A Reduces Sleep Deprivation-Related Behavior Problems and Aging Signs by Blocking Cell Death Processes Through Cryptochrome 1
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Abstract
Ganoderic acid A (GAA) significantly ameliorated sleep deprivation-induced cognitive decline and affective deficits in a mouse model.
- GAA reversed the dysregulation of proteins related to ferroptosis, such as SLC7A11, GPX4, and ACSL4.
- The compound also inhibited pyroptosis by targeting the NLRP3-caspase-1-GSDMD signaling pathway.
- GAA significantly increased the expression of Cryptochrome 1 (Cry1), which is linked to its protective effects.
- In Cry1-deficient mice, the neuroprotective effects of GAA were notably reduced.
- A stable interaction between GAA and Cry1 was indicated by surface plasmon resonance and molecular dynamics simulations.
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