TABLE 1.

The role of Foxo3a in major models of COI was summarized.

Diseases	Model in vivo or in vitro	Downstream pathway	Biological functions	Potential effect on COI	References
AD	Apoe4 mice	Foxo3a upregulates the expressions of autophagy and mitophagy	Foxo3a ameliorates neuroinflammation	↑	Sohn et al., 2021; Zhou et al., 2024
	Aβ-stimulated neurons	Foxo3a upregulates expressions of bim, puma and caspases-3	Foxo3a induces apoptosis of neurons	↓	Sanphui and Biswas, 2013; Akhter et al., 2014; Saha and Biswas, 2015
Stroke	MCAO/R rats	Foxo3a alleviates mitochondrial oxidative damage through increasing MnSOD expression	Foxo3a inhibits neurological damage	↑	Xie et al., 2022
	MCAO/R rats	Foxo3a suppressed the expressions of BRCC3 and NLRP3	Foxo3a alleviates oxidative stress and neuroinflammatory responses	↑	Tan et al., 2024
	tMCAO rats	Foxo3a promotes the activity of CREB factor	Foxo3a attenuates neuroinflammatory responses	↑	Chen B. et al., 2023
IBI	Ovariectomized female rats	High expression of Foxo3a is accompanied by high level of caspase-3	Foxo3a induces apoptosis of neurons	↓	Jover-Mengual et al., 2010
	Hypoxia-ischemia rats	Foxo3a upregulates the expressions of bim and caspase-3	Foxo3a triggers apoptosis of neurons	↓	Li et al., 2009, 2013, 2017
	Cerebral I/R mice	Foxo3a promotes the ROS production	Foxo3a reduces apoptosis and excessive ERS	↑	Shi et al., 2019
	Cerebral I/R rats	Foxo3a suppressed the activation of nrf2/glutathione signaling pathway	Foxo3a potentially reduces neuronal survival	↓	Zaki et al., 2022
	Cerebral I/R rats	Foxo3a inhibits the activation of NF-κB signaling pathway	Foxo3a alleviates neuroinflammatory responses	↑	Tan et al., 2021
	OGD-stimulated neurons	Foxo3a upregulate the expression of bax, cleaved caspase 3, but reduces the level of bcl-2	Foxo3a protect against neuronal cell injury	↑	Meng et al., 2022
PA	Dopaminergic neuronal PC12 cells	Foxo3a activates the autophagy	No significant effect of Foxo3a on neuronal viability	Unknown	He et al., 2022
	MPTP mice	Increased level of Foxo3a is accompanied by increased level of MnSOD/NQO1/HO-1, but decreased NF-κB pathway	Foxo3a potentially rescues the loss of dopaminergic neurons	↑	Leem et al., 2024
	MPTP mice	Foxo3a upregulate the expression of bim	Foxo3a inhibits the apoptosis of neuron	↑	Liu L. et al., 2014
	6-hydroxy dopamine-treated cells and rats	Foxo3a promotes the expression of puma and FasL	Foxo3a triggers neuron death	↓	Sanphui et al., 2020; Bhattacharyya et al., 2023
TBI	Mice treated with weight drop	Acetylation of Foxo3a increased the level of bim	Acetylation of Foxo3a triggers apoptosis of neuron	↓	Xu et al., 2024
	Mice struck by convex tip	Foxo3a transcriptionally upregulates AQP4	Foxo3a leads to cytotoxic edema	↓	Kapoor et al., 2013
	Mice treated with weight drop	Foxo3a activates autophagy	Foxo3a initiates neuronal damage in the hippocampus	↓	Sun et al., 2018

MCAO/R, middle cerebral artery occlusion/reperfusion, tMCAO, transient middle cerebral artery occlusion, IBI, ischemic brain injury, OGD, oxygen-glucose deprivation, MPTP, methyl-4-phenyl-1,2,3,6-tetrahydropyridine, AQP4, Aquaporin 4. “↑” represents promotion of COI, “↓” represents inhibition of COI.