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Published on: October 20, 2023
Ganoderic Acid A Mitigates Sleep Deprivation-Induced Behavioral Deficits and Aging-like Phenotypes by Cryptochrome
Yuchen Ma1, Peiyuan Sun2, Lihui Feng3
1College of Food Science and Technology, Jiangnan University, Wuxi214122, China.
Abstract:
Sleep deprivation (SD) is closely linked to affective disorders, cognitive impairment, and accelerated neuroaging. Using an SD mouse model, we examined the neuroprotective effects of Ganoderic acid A (GAA), focusing on ferroptosis, pyroptosis, and their potential regulation by Cryptochrome 1 (Cry1). GAA significantly ameliorated SD-induced affective deficits, cognitive decline, and aging-like phenotypes. Mechanistically, GAA reversed SD-induced dysregulation of ferroptosis-related proteins (SLC7A11, GPX4, and ACSL4, etc.), and concurrently suppressed pyroptosis by inhibiting the NLRP3-caspase-1-GSDMD signaling cascade. Notably, GAA significantly upregulated Cry1 expression, and the protective effects of GAA were substantially diminished in Cry1-deficient mice. Furthermore, surface plasmon resonance and molecular dynamics simulations demonstrated a stable interaction between GAA and Cry1, which may underlie the GAA-induced upregulation of Cry1. Collectively, these findings suggest that Cry1 is involved in the regulation of GAA-associated protective effects against SD-induced neurobehavioral disturbances and neuroaging via suppression of ferroptosis and pyroptosis.
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