Why does FOXO activation through AKT inhibition promote neurogenesis when FOXO typically suppresses cell proliferation?

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Description

The study shows WTJD inhibits AKT phosphorylation to activate FOXO4, promoting hippocampal neurogenesis. This contradicts established knowledge that FOXO transcription factors generally inhibit cell cycle progression and proliferation. The mechanistic basis for this apparent contradiction in neural stem cells requires clarification.

Gap type: contradiction Source paper: Wenyang-Tianjing-Jieyu decoction ameliorates Kidney-Yang deficiency type depression-like behavior in Sprague-Dawley rats by enhancing neurogenesis via the FOXO signaling pathway. (2026, Journal of ethnopharmacology, PMID:41475623)

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